bluuebunny/crossref_metadata_2025 huggingface dataset:
Mast Cell Histamine-Releasing Activity from Stimulated Rat Neutrophils
Authors: Cochrane David E. , Boucher William , Carraway Robert E.
Published: August 2009

Mast cell histamine-releasing activity (HRA) has been observed in medium derived from stimulated rat neutrophils pretreated with cytochalasin B. This HRA did not require cell-cell contact between mast cells and neutrophils, and its concentration was increased by increasing the number of neutrophils or by raising the concentration of chemotactic peptide used to stimulate the neutrophils. The HRA survived boiling for 5 min and storage overnight at ––20°C. In the absence of neutrophil stimulation, no HRA was observed.
Flow Cytometric Analysis of Lymphocyte Populations in Guinea Pig Blood and Spleen
Authors: McPhee Catriona A. , Milton James I. , Thomson Angus W.
Published: August 2009

A panel of novel mouse monoclonal antibodies was used, in an indirect immunofluorescence procedure, to identify subsets of guinea pig lymphoid cells which were quantified by now cytometric analysis. The staining characteristics of the antibodies were also examined by alkaline phosphatase-anti-alkaline phosphatase staining of cryostat sections of spleen and cytocentrifuge preparations of blood and spleen mononuclear cells. The values obtained for T and B cell populations were similar to those previously described using rosetting procedures, and the study also confirmed the high incidence of constitutive la antigen expression on guinea pig lymphocytes. Compared with animals receiving immunization (ovalbumin) alone, guinea pigs treated with ciclosporin A showed only minor changes in lymphocyte subsets, whereas those pretreated with cyclophosphamide revealed striking reductions in circulating T and B lymphocytes and in splenic B cells. Both ciclosporin A and cyclophosphamide markedly reduced la antigen expression on lymphocytes in blood, whilst cyclophosphamide also inhibited la antigen expression in the spleen.
Influence of an Hymenolepis diminuta Infection on IgE and IgA Bound to Mouse Intestinal Eosinophils
Authors: Van der Vorst E. , Dhont H. , Cesbron J.Y. , Capron M. , Dessaint J.P. , Capron A.
Published: August 2009

Infection of mice with Hymenolepis diminuta, which is an ‘exclusively’ intestinal cestode, affects the number of eosinophils and noneosinophilic cells with IgE or IgA on their surface in the lamina propria. Presence of IgE on eosinophils is basically a primary infection response, while after reinfection the response is primarily characterized by IgA. For IgE- as well as for IgA-bearing eosinophils the response is most abundant in the second quarter of the intestine which is the parasite’s preferred habitat. For non-eosinophilic cells the effect is smaller and limited to the IgE-bearing cells, with the most significant effect in the second quarter of the intestine.
Augmentation of Leukotriene C4 Production by Gamma Interferon in Leukocytes Challenged with an Allergen
Authors: Saito Hiroshi , Hayakawa Tetsuo , Mita Haruhisa , Yui Yasuo , Shida Takao
Published: August 2009

Leukocytes from mite-sensitive asthmatic patients were challenged with an allergen and the supernatant assayed for histamine, immunoreactive leukotriene C4 (i-LTC4), and γ-interferon (γ-IFN). In addition, the concentration of γ-IFN in the plasma of patients with bronchial asthma was assayed. Significantly higher concentrations (p <0.01) of γ-IFN were detected in patients’ plasma (0.27 ± 0.32 U/ml, n = 61) than in that of healthy controls (0.04 ± 0.06 U/ml, n = 19). The leukocytes produced 7.3 ± 6.7 ng of i-LTC4/106 basophils (n = 32), and histamine release was 41.1 ± 37.1% of total histamine. There was a significant correlation (p <0.01) between the capacity of leukocytes to release i-LTC4 and γ-IFN. The capacity of leukocytes to release histamine and to produce γ-IFN was not significantly correlated (r = 0.263). About twice as much i-LTC4 was generated from leukocytes pretreated for 24 h with 0.1–1.0 U/ml of recombinant human γ-IFN, but histamine release was not changed. Another type of IFN, α-IFN, did not alter the capacity of leukocytes to release histamine as well as γ-IFN upon preincubation for 24 h at 1–1,000 U/ml. Pretreatment with 1–10 U/ml of β-IFN slightly enhanced the capacity upon challenge with 10 ng/ml of mite allergen. The enhancing effect of γ-IFN on i-LTC4 generation was decreased by treatment with H-7, a nonspecific inhibitor of protein kinase C activity. The capacity of leukocytes to produce γ-IFN and i-LTC4 was enhanced by treatment with phorbol myristate acetate. W-7, a calmodulin antagonist, dose dependency inhibited the production of both γ-IFN and i-LTC4 in the allergen-stimulated leukocytes. AA-861, a selective inhibitor of 5-lipoxygenase, inhibited the production of both γ-IFN and i-LTC4. From these findings, it is assumed that the activation of protein kinase C by treatment with γ-IFN is closely related to the enhancement of i-LTC4 production. In addition, the generation of 5-lipoxygenase products, such as i-LTC4, is closely connected with the production of γ-IFN in allergen-stimulated leukocytes.
The Effect of Thyroxine on Spontaneous Thyroiditis in BB/W Rats
Authors: Banovac K. , Ghandur-Mnaymneh L. , Zakarija M. , Rabinovitch A. , McKenzie J.M.
Published: August 2009

The effect of T4 on the incidence of lymphocytic thyroiditis and on titers of antibodies to thyroglobulin and thyroid microsomal antigen was studied in BB/W rats that are prone to develop spontaneously autoimmune thyroiditis and diabetes. Thirty-three animals were separated in two groups. Rats in one group had 1 mg T4 per liter of drinking water, and the other group was given no T4. After 3–4 months of therapy the T4-treated group had a reduced production of antibody to thyroglobulin (p <0.05) and to microsomal antigen (p <0.005) and a significantly lower frequency of lymphocytic thyroiditis (p <0.05). Our data are consistent with previous findings in experimentally induced thyroiditis in rats and suggest that T4 has an immunosuppressive effect.
Eosinophil Granule Proteins in Serum after Allergen Challenge of Asthmatic Patients and the Effects of Anti-Asthmatic Medication
Authors: Venge Per , Dahl Ronald , Peterson Christer G.B.
Published: August 2009

Thirteen allergic asthmatic patients were challenged six times each and serum levels of ECP (eosinophil cationic protein), EPX (eosinophil protein-x) and blood counts of eosinophil granulocytes were measured in blood obtained before and at regular intervals after challenge. Three challenges were performed in a blinded and randomized fashion and included a one-dose pretreatment with the inhalant anti-asthmatic drugs disodium cromoclycate, terbutaline and budesonide. One challenge was performed after 4 weeks’ pretreatment with the inhalant budesonide and one was a histamine challenge. Pre-challenge levels of ECP were significantly reduced both after 4 weeks and after a one-dose treatment with budesonide whereas the EPX levels were reduced only after the former. Blood eosinophil counts were unaffected by the challenge whereas the ECP levels were significantly reduced after the placebo challenge and when premedicated with disodium cromoglycate and terbutaline. The EPX levels stayed unaltered at the placebo challenge but were significantly reduced when the patients were premedicated with terbutaline. ECP and EPX levels as well as blood eosinophil counts before challenge were significantly related to the development of the late asthmatic reaction. The results again focus on a relation between the eosinophil granulocyte and asthma and suggest that an increased activity of the blood eosinophil, as suggested by the raised serum levels of the granule proteins ECP and EPX, is one prerequisite for the development of chronic asthma.
Enhanced Murine Respiratory Tract IgA Antibody Response to Oral Influenza Vaccine when Combined with a Lipoidal Amine (Avridine)
Authors: Bergmann Karl-Christian , Waldman Robert H.
Published: August 2009

The adjuvant activity of avridine, a synthetic lipoidal amine, incorporated in liposomes, was studied in mice immunized orally with killed influenza virus vaccine (A/PR/8/34, H1N1). Coadministration of avridine-containing liposomes and viral antigen enhanced the remote-site IgA antibody response in the respiratory tract without a concomitant serum antibody response or side effects. The results support the possible use of mucosal adjuvants for oral immunization against respiratory pathogens.
Antigenic Contraction of Guinea Pig Tracheal Preparations Passively Sensitized with Monoclonal IgE: Pharmacological Modulation
Authors: Haye-Legrand Isabelle , Norel Xavier , Labat Carlos , Benveniste Jacques , Brink Charles
Published: August 2009

Spirally cut guinea pig tracheal preparations were passively sensitized using a mouse monoclonal IgE antibody against dinitrophenol (DNP). Maximal contraction observed following challenge with DNP-bovine serum albumin (DNP-BSA, 5 μg/ml; n = 20) response was approximately 46% of the histamine response (0.52 ± 0.09 g/mm2; n = 53). Indomethacin (1.7 μM) increased and PGE2 (1 μM) decreased the response to the antigen. FPL 55712 (10 μM), atropine(0.1 μM), L 651392 (5 μM) or tripelennamine(1 μM) always reduced the maximal DNP-BSA response, but not BN 52021 (100 μM). This model may be used for rapid detection of compounds with antiallergic properties on IgE-dependent lung pathological states.
Regulation of the Immune Response to Allergens by Immunosuppressive Allergenic Fragments
Authors: Litwin Allen , Pesce Amadeo J. , Michael Gabriel
Published: August 2009

Nine patients with anaphylactic sensitivity to honey bee venom (HBV) were treated with P-1, a pepsin derived fragment of HBV phospholipase A2 (PLA2). P-1 caused only rare reactions with doses of 100 μg/injection. Treatment resulted in a substantial decrease in specific anti-PLA2 IgE and IgG antibodies as well as a decline in skin test sensitivity to PLA2. Another group of HBV-sensitive patients was treated with unaltered PLA2. Doses greater than 20 μg/injection were not tolerated. PLA2 injections caused an increase in anti-PLA2 IgG and IgE antibodies as well as increase in skin test sensitivity. This study demonstrates that a non-immunogenic fragment derived from an allergen can downregulate immune responses and thus offer a new modality for therapy of allergic diseases.
The Significance of Complement Activation in the Pathogenesis of Hypersensitivity Pneumonitis: Sequential Changes of Complement Components and Chemotactic Activities in Bronchoalveolar Lavage Fluids
Authors: Yoshizawa Yasuyuki , Nomura Akihiro , Ohdama Shinichi , Tanaka Motoichi , Morinari Hajime , Hasegawa Shizuo
Published: August 2009

Hypersensitivity pneumonitis (HP) is believed to be induced by immunological mechanisms, the details of which remain to be clarified. While a role for cellular immunity is accepted in the pathogenesis of HP, several clinical observations also suggest a role for immune-complex-mediated lung injury. We have previously demonstrated the presence of chemotactic factors for polymorphonuclear cells (PMNs) in bronchoalveolar lavage (B AL) fluids of acutely ill patients with the summer type of HP found in Japan. The present study correlated chemotactic factors for PMNs with the level of C5a des Arg in BAL fluids obtained from patients with summer type HP. Furthermore, this study demonstrated that PMNs were increased in BAL fluids obtained after 2 days of avoidance of exposure to the presumptive causative agent. The percentage of PMNs in the BAL increased in proportion to the activity of the chemotactic factors. Finally, leukotriene B4 was not detected in concentrated BAL or supernatant fluids of cultured macrophages. These results suggest that complement activation in the respiratory tract may occur as the early event in the pathogenesis of HP.
Production of Interleukin-1 in Macrophage Cultures from Rats with Nephrotoxic Serum Nephritis
Authors: Matsumoto Koichi
Published: August 2009

To investigate the role of cell-mediated immunity in the pathogenesis of experimental glomerulonephritis, we examined interleukin-1 (IL-1) activity in the culture supernatant of lipopolysaccharide-stimulated peritoneal macrophages from rats with an accelerated autologous form of nephrotoxic serum nephritis (NTSN). Modified NTSN was produced by an intravenous injection of nephrotoxic serum (NTS) into the rats which had previously been immunized with rabbit IgG and Freund’s complete adjuvant. It was found that the NTSN rats had significantly increased levels of IL-1 activity when compared to the values obtained with normal controls and the other control group, consisting of pre-immunized rats (rabbit IgG), then given normal rabbit globulin instead of NTS. The administration of a rabbit anti-rat macrophage serum reduced the production of IL-1 activity in the NTSN rats. In this experimental model IL-1 synthesis by peritoneal macrophages is present early in the disease process and may be an important mediator of glomerular immune injury.
Budesonide Reduces Sensitivity to Antigen but Does Not Alter Baseline Tone or Responsiveness to Carbachol, Terbutaline, and Enprofylline in IgE-Sensitized Guinea-Pig Tracheae
Authors: Persson C.G.A. , Andersson P.T. , Gustafsson B.
Published: August 2009

In vitro incubation of IgE-sensitized guinea-pig tracheal rings with 10––7M budesonide for 24 h significantly shifted the concentration-response curve to antigen by 5-fold to the right. Smooth muscle characteristics such as baseline tone, muscarinic contraction or relaxation to β2-receptor agonists and xanthines were not or only marginally affected by this exposure of airway tissue to a glucocorticoid drug. It is concluded that budesonide reduced anaphylactic IgE-driven release of contractile mediators.
Effect of Cyclophosphamide Pretreatment on Defective Delayed-Type Hypersensitivity in Autoimmune-Prone MRL Mice
Authors: Okuyama Harue , Matsunaga Takashi , Kobayashi Sei-ichi , Hashimoto Yoichi , Kawaguchi Yoshinori , Yamamoto Ken-ichi
Published: August 2009

Autoimmune MRL mice develop a poor delayed-type hypersensitivity (DTH) after BCG cell wall (BCG CW) immunization. To test the possible participation of suppressor cells on DTH induction, MRL/ MpJ-lpr/lpr (MRL-lpr) and MRL/MpJ-+/+ (MRL-+/+ ) mice were pretreated with cyclophosphamide (Cy) 4 days before the immunization. The footpad reaction to the purified protein derivative of tuberculin (PPD) was enhanced remarkably by Cy pretreatment in both MRL-lpr and MRL-+/+ mice. In addition, the lymph node cells obtained from nonpretreated MRL-lpr and MRL- +/+ mice at 7 days after BCG CW immunization suppressed the DTH induction of Cy-pretreated MRL-+/+ mice. On the other hand, a positive proliferative response to PPD in vitro was seen only in the cells from Cy-pretreated MRL-+/+ and younger MRL-lpr mice, but not in the cells of nonpretreated MRL-+/+ or both pretreated and nonpretreated older MRL-lpr mice. Removal of B220-positive cells from the lymph node cell populations of Cy-pretreated MRL-lpr mice restored PPD responsiveness, but the same treatment had no effect on the cells from nonpretreated MRL-lpr mice. The results suggest that DTH responses to PPD in MRL mice immunized with BCG CW are regulated by Cy-sensitive suppressor cells. These suppressor cells occur in MRL mice irrespective of whether they carry the lpr gene. And it is also demonstrated that MRL-lpr mice have TDTH precursor cells in a sufficient number for TDTH production even after expressing lymphadenopathy.
Comparative Analysis of Physicochemical and Immunochemical Properties of the Two Major Allergens from Dermatophagoides pteronyssinus and the Corresponding Allergens from Dermatophagoides farinae
Authors: Yasueda Hiroshi , Mita Haruhisa , Yui Yasuo , Shida Takao
Published: August 2009

Two major allergens, DPI (Der p I) and DP2 (Der p II), were isolated from the whole culture extract of Dermatophagoides pteronyssinus, and the physicochemical and immunochemical properties of these allergens were compared with those of the corresponding allergens from Dermatophagoides farinae, DF1 (Der f I)and DF2 (Der f II).On sodium dodecyl sulfate-polyacrylamide gel electrophoresis, polyacrylamide gel isoelectric focusing and amino acid analysis, both DP1 and DP2 were demonstrated to have close physicochemical similarity with DF1 and DF2, respectively. On immunodiffusion with the use of rabbit antisera, the two Der I allergens showed the reaction of typical partial identity, while the two Der II allergens showed the reaction of almost complete identity. Radioallergosorbent test (RAST) and RAST absorption experiments with the use of sera from mite-allergic patients showed that human IgE antibody response to the Der I allergens was directed against both cross-reactive and species-specific determinants. In contrast, IgE antibodies to the Der II allergens were demonstrated to react almost completely to cross-reactive determinants.
Quantitative Rather than Qualitative Differences between Monocytes with Respect to IgE Fc Receptor Expression as Studied by Flow Cytofluorometry
Authors: Hed J. , Halldén G. , Johansson S.G.O. , Larsson P.
Published: August 2009

In this study we have used aggregated human IgE, conjugated with fluoroisothiocyanate, as a ligand in flow cytofluorometry to detect the low-affinity Fc receptor for IgE on human leukocytes. The percentage of IgE-binding monocytes increased up to 44%, in a dose-related manner, as the concentration of aggregated IgE in the fluid phase increased to the highest concentration (300 μg/ml) used in this study. No such dose-related increase was shown for granulocytes (1.8% IgE-binding cells) or lymphocytes (2.1 % IgE-binding cells). The IgE-binding was inhibited by IgE but not by IgG, whereas the opposite effect was obtained for IgG binding. We could not verify a distinct IgE-binding subpopulation of monocytes in peripheral blood. The results rather indicate that most monocytes bind IgE to a variable degree depending on the concentration of the ligand in the fluid phase.
Detection of Antigens from Gram-Negative Bacilli in Urine of Children with Urinary Tract Infections
Authors: Kim Dong Soo , Gorzynski Eugene A. , Milgrom Felix
Published: August 2009

Enterobacterial common antigen (ECA) has attracted considerable interest since the original publication by Kunin in 1962. In the present study we demonstrated this antigen directly in the urine from patients with urinary tract infections (UTI) elicited by enterobacteria. Sheep erythrocytes were incubated with UTI urine; this resulted in their coating with ECA, which was studied by means of hemagglutination by anti-ECA serum. Test tube hemagglutination and the more simple slide hemagglutination were employed and with both procedures similar results were obtained. Positive results were observed in 94–99% of urine specimens from enterobacterial UTI collected in The Buffalo Children’s Hospital in the 1960s. ECA in urine could also be demonstrated by hemagglutination inhibition. In this test, antibodies in anti-ECA serum were neutralized as a result of incubation of this serum with urine, and agglutination by the antiserum of sheep erythrocytes coated with a standard ECA preparation was prevented or reduced. By means of this latter test, ECA could be demonstrated in 67–88% of urine specimens from enterobacterial UTI. The possible diagnostic application of these tests has been discussed.
Potentiation of the Stimulatory Capacity of Pokeweed Mitogen via Its Binding to Autologous Erythrocytes
Authors: Uiterdijk H.G. , Doekes G. , de Vreede T.M. , de Vries E. , Cats A.
Published: August 2009

The effect of human erythrocytes (E) on blastogenesis and immunoglobulin (Ig) production induced by pokeweed mitogen (PWM) in cultures of human peripheral blood mononuclear cells (PBMC) was investigated. The stimulation of PBMC with PWM was markedly enhanced in the presence of E, and PWM bound to E, followed by thorough washing (E-PWM), was even more effective in inducing blast cell formation and Ig production. Blast cell responses after stimulation with E-PWM were on average two times higher than those seen after stimulation with comparable dilutions of fluid-phase PWM. The PWM that remained in solution after incubation with E (Sup E-PWM) had little mitogenic capacity and inhibited the blast cell response induced by fluid-phase PWM. Transwell® culture experiments demonstrated that the enhancement of the blast cell response of PBMC by E-PWM could be induced by PWM that was released from E-PWM, whereas the enhancement of Ig production was found to be dependent on the presence of PWM on E. Both for blast cell formation and Ig production, it was found that the enhanced stimulation with E-PWM depended on the presence of monocytes.
Effect of Eicosapentaenoic Acid Rich Menhaden Oil and MaxEPA on the Autoimmune Disease of Mrl/l Mice
Authors: Westberg Gunnar , Tarkowski Andrej , Svalander Christian
Published: August 2009

The Mrl lpr/lpr (Mrl/l) mouse is a model for systemic lupus erythematosus and rheumatoid arthritis in humans. The diet of Mrl/l mice was supplemented with EPA (see Introduction) in menhaden oil or in the commerical fish oil MaxEPA. The survival of mice was not affected by the dietary manipulations. The addition of menhaden oil decreased the severity of the renal pathology. However, MaxEPA containing the same amount of eicosapentaenoic acid was considerably less effective. A diet deficient in polyunsaturated fatty acids did not ameliorate any manifestations of the disease. Anti-DNA antibody levels in serum were not influenced by the therapy. Myocardial abscesses and/or ulcerating valvular lesions were observed in about one third of the mice, irrespective of the diet given.
Effects of Combined Receptor Antagonists of Leukotriene D4(LTD4) and Platelet-Activating Factor (PAF) on Rhesus Airway Responses to LTD4, PAF and Antigen
Authors: Patterson Roy , Harris Kathleen E. , Bernstein Peter R. , Krell Robert D. , Handley Dean A. , Saunders Robert N.
Published: August 2009

Rhesus monkeys with IgE-mediated asthmatic-type responses to Ascaris suum antigen were pre-treated with a combination of 2 receptor antagonists to leukotriene D4 (LTD4) and platelet-activating factor (PAF). This combination of anti-LTD4 and anti-PAF was shown to inhibit airway responses to either LTD4 or PAF in separate experiments in these Ascaris airway-reactive animals. When the same combination of LTD4 and PAF receptor antagonists was used to pretreat the same animal prior to aerosol challenge with Ascaris antigen we could not demonstrate inhibition of the antigen-induced airway response. Thus, combined receptor blockade for LTD4 and PAF did not alter IgE-mediated acute airway responses to antigen in this species. We review the current status of rhesus asthma and LTD4 and PAF receptor antagonist activity in this model.
Regulation of the IgE Antibody Response
Authors: Ishizaka Kimishige
Published: August 2009

The IgE synthesis is regulated by T cell derived IgE-binding factors in an isotype-specific manner. The IgE-potentiating and IgE-suppressive factors may share common structural genes; therefore, a common polypeptide chain and their biologic activities are determined by posttranslational glycosylation processes. Under the physiological conditions, the carbohydrate moieties in the IgE-binding factors formed by a subset of T cells are determined by the ratio between two T cell factors, i.e., glycosylation-enhancing factors and glycosylation-inhibiting factors (GIF), in their environment. GIF is an immunosuppressive lymphokine. Repeated injections of this lymphokine into antigen-primed mice facilitated the generation of antigen-specific suppressor T cells and suppressed both IgE and IgG antibody responses. This effect of GIF was reproduced in vitro. Activation of antigen-specific T cells by antigen-pulsed macrophages, followed by propagation of the antigen-activated T cells by interleukin 2 in the presence of GIF resulted in the generation of suppressor T cells which produced antigen-specific GIF upon antigenic stimulation. Some of the T cell hybridomas constructed from the antigen-specific suppressor T cells formed antigen-specific GIF upon antigenic stimulation. The antigen-specific GIF formed by the T cell hybridoma share several common properties with antigen-specific suppressive factor and suppressed the antibody response of syngeneic mice in a carrier-specific manner. The results obtained with mouse lymphocytes suggest a maneuver to suppress the IgE antibody formation to an allergen in atopic patients.
Emerging Picture of the Receptor with High Affinity for IgE
Authors: Metzger H. , Blank U. , Kinet J.-P. , Kochan J. , Ra C. , Rivera J. , White K.
Published: August 2009

The cDNAs for two of the subunits of the receptor with high affinity for IgE have been isolated and sequenced. That for the IgE-binding alpha subunit predicts a polypeptide with a single transmembrane segment. The predicted extracellular amino terminal portion, comprised of 180 residues, is homologous to the corresponding region of Fcγ receptors and contains two truncated immunoglobulin-like domains. The cDNA for beta predicts a peptide with four transmembrane segments, but its sequence is unrelated to known proteins. Experiments to isolate the cDNA for the gamma subunit have begun; when completed, cotransfection of the three genes will be attempted to get expression, a process that has not so far been successful for the individual subunits. Such expression will permit further analysis of the receptor’s function and ultimately may provide information on how best to intervene clinically in the activation of mast cells and basophils.
Human FcεR II and IgE-Binding Factors
Authors: Delespesse G. , Sarfati M. , Hofstetter H. , Frost H. , Kilchherr E. , Suter U.
Published: August 2009

The low-affinity receptor for IgE (FcεR II) is mainly expressed on B lymphocytes, although it may also be found on some monocytes, eosinophils, and platelets. The presence of FcεR II on T cells is still controversial, but our results demonstrate that it is expressed on some HTLV-I-transformed T lymphocytes, and they strongly suggest that it may be found on a small proportion of normal T cells. FcεR II is a 45-KD glycoprotein containing one N-linked carbohydrate of complex type, O-linked carbohydrates, and sialic acid residues. Fc II is cleaved into soluble fragments with molecular weights of 37, 33, 25, and 12 KD, the first three retain the ability of binding to IgE, i.e., they are IgE-binding factors (IgE-BFs). The enzymes involved in their proteolytic cleavage are cell bound. The cDNA coding for FcεR II was cloned and functionally expressed. The predicted sequence has no homology with that of murine IgE-BFs which are of T cell origin. However, there is a striking homology with several animal lectins, and since the IgE-binding site is located in the homology region, it is possible that it binds to IgE via the carbohydrates expressed on the Fc region of this immunoglobulin. The expression of FcεR II on B cells and the release of IgE-BFs are upregulated by interleukin 4 and suppressed by gamma and alpha interferons. The finding that FcεR II is identical to CD23, known as a B cell activation marker, suggests that FcεR II or its soluble fragments are involved in B cell activation. Accumulating evidence suggests that some soluble fragments of FcεR II display B cell growth factor activity. Finally, several observations strongly suggest that IgE-BFs regulate human IgE synthesis.
Interaction of IgE with Its High-Affinity Receptor
Authors: Baird Barbara , Shopes Robert J. , Oi Vernon T. , Erickson Jon , Kane Patricia , Holowka David
Published: August 2009

Structural interactions between IgE and its high-affinity receptor have been investigated with the methods of fluorescence resonance energy transfer and genetic engineering. The results indicate that IgE has a bent conformation when bound to receptor on the cell surface and that the site of interaction is contained in the Cε2 and Cε3 domains; the C-terminal domain, Cε4, is not required for binding. Cross-linking of IgE-receptor complexes is required for signal transduction across the plasma membrane. Binding studies with defined bivalent ligands indicate that structural and/or kinetic features determine the functional effectiveness of the cross-linked states.
Involvement of Tumour Necrosis Factor and Other Cytokines in Immune-Mediated Vascular Pathology
Authors: Grau Georges E. , Piguet Pierre-François , Vassalli Pierre , Lambert Paul-Henri
Published: August 2009

Vascular endothelial cells are actively involved in coagulation and inflammation processes and appear to represent a important element in cell-mediated immune responses. In this paper, the possible role of endothelial cells as a target for immunopathological reactions was analyzed. Experimental neurovascular lesions were studied in a model of cerebral malaria, with particular attention to the role of cytokine interactions in vivo.
Granulocyte/Macrophage Colony Stimulating Factor
Authors: Morrissey Philip J. , Grabstein Kenneth H. , Reed Steven G. , Conlon Paul J.
Published: August 2009

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a well-characterized hematopoietic growth factor. Recently, using purified recombinant-derived material, we have found that GM-CSF is also a potent activator of mature functional macrophages. Thus, we have found that exogenous GM-CSF augments the primary plaque-forming response to sheep red blood cells and that this effect is due to upregulation of la antigen expression and interleukin 1 production by the macrophages. We also show that GM-CSF inhibits the replication of Trypanosoma cruzi in cultured peritoneal macrophages and causes an accelarated clearance of Salmonella typhimurium from the peritoneal cavity of mice. These data indicate that GM-CSF is a multifunctional molecule stimulating both hematopoiesis and mature macrophage function.
Preferential Differentiation of Inflammatory Cells by Recombinant Human Interleukins
Authors: Ishizaka Teruko , Saito Hirohisa , Hatake Kiyohiko , Dvorak Ann M. , Leiferman Kristin M. , Arai Naoko , lshizaka Kimishige
Published: August 2009

The effects of recombinant human interleukins (IL) on hematopoiesis were explored by using suspension cultures of mononuclear cells of human umbilical cord blood and bone marrow cells. The results showed that IL-5 induced the selective differentiation and proliferation of eosinophils. After 3 weeks in culture with IL-5, over 90% of nonadherent cells in both bone marrow cell and cord blood cell cultures became eosinophilic myelocytes. Culture of the same cells with IL-4 resulted in the selective growth of OKT-3+ lymphocytes. In suspension cultures of bone marrow cells and cord blood cells grown in the presence of IL-3, basophilic, eosinophilic, and neutrophilic myelocytes developed within 2 weeks. By 3 weeks, however, the majority of non-adherent cells became eosinophilic myelocytes. In contrast to mouse bone marrow cell cultures, neither IL-3 nor combination of IL-3 and IL-4 induced the differentiation of mast cells in human bone marrow or cord blood cell cultures.
Cells and Secretagogues Involved in the Human Late-Phase Response
Authors: Charlesworth Ernest N. , Iliopoulos Othon , MacDonald Susan M. , Kagey-Sobotka Anne , Lichtenstein Lawrence M.
Published: August 2009

Those scientists interested in allergic inflammatory processes have recently been focusing on the late-phase response, since it appears most similar to the chronic disease states observed in allergic patients. In this review we will focus on the pattern of mediator release and cellular traffic observed in two in vivo human models of the late-phase reaction, one involving the upper airways and the other the skin. We have observed in these models, as had been observed earlier in blood, that the late-phase reaction is associated with a second increase in the level of mediators. We also describe our studies of the secretagogues responsible for this late-phase mediator release and, in so doing, introduce the subjects of histamine-releasing factors and IgE heterogeneity.
Interaction of Neuropeptides with Human Mast Cells
Authors: Church Martin K. , Lowman Mark A. , Robinson Clive , Holgate Stephen T. , Benyon Christopher
Published: August 2009

Mast cells of human skin, but not lung, adenoids, tonsils, or intestine, release histamine in response to substance P, vasoactive intestinal polypeptide, and somatostatin. The substance P receptor of skin mast cells is not of the NK-1, NK-2 or NK-3 subtypes of smooth muscle. Time course and calcium dependency of release by peptides differed from anti-IgE. With anti-IgE, the molar ratios of histamine:PGD2:LTC4 generated by skin mast cells was 1,000:25:2, whereas with substance P these ratios were 1,000:1:0.1. Similar results were obtained with the other neuropeptides. The ability of peptides to stimulate skin mast cell histamine release suggests a mechanism whereby their release from dermal nerve endings is coupled to changes in micro-vasculature.
The Third Histamine Receptor
Authors: Arrang J.M. , Garbarg M. , Lancelot J.C. , Lecomte J.M. , Pollard H. , Robba M. , Schunack W. , Schwartz J.C.
Published: August 2009

The third histamine receptor was first identified on brain neurons and seems also to be present in other cells such as the lung mast cells. Hence the novel and potent H3 receptor agonist (R)-α-methylhistamine might find therapeutic applications in allergic diseases
Structure-Activity Relationships and Effects of Platelet-Activating Factor Antagonists in the Hetrazepine Series
Authors: Weber Karl Heinz , Heuer Hubert
Published: August 2009

Thieno-triazolo-1,4-diazepines (hetrazepines) antagonize platelet-activating factor (PAF) induced platelet aggregation and inhibit the binding of [3H]-PAF. Introduction of a carboxamide alkyl side chain into the thiophene ring leads to compounds with less affinity to the benzodiazepine receptor and without sedative effects on the central nervous system (e.g., WEB 2086). By ring closure of the side chain, new tetracyclic compounds have been obtained. A parabolic relationship between either [3H]-PAF binding or PAF activity and the bulkiness of the alkyl substituents to the triazolo ring of the hetrazepines or of the bulkiness the 2-acyl moiety of the PAF analogues was found in quantitative structure-activity relationships. This suggests that perhaps the alkyl substituent of the hetrazepines fits the same receptor pocket as the 2-acyl moiety of the PAF agonists.
Usefulness of Bronchoalveolar Lavage in Asthmatics
Authors: Michel F.B. , Godard Ph. , Bousquet J.
Published: August 2009

Bronchoalveolar lavage (BAL) has been studied in asthmatic patients; it is a well-tolerated procedure and can be used in clinical practice to evaluate individual patients. However, the main question is: Does BAL contribute to a better understanding of the pathophysiology of bronchial asthma? The arguments in favour are as follows: (1) experiments in monkeys, indicating that the cells recovered by BAL contribute to the triggering of asthma; (2) demonstration of inflammatory cell (eosinophils, neutrophils, and lymphocytes) influx after allergen inhalation challenge, and (3) in vitro demonstration of cellular activation corresponding with clinical symptoms. BAL offers a new approach to the understanding of asthma. There is a lot of unresolved questions which should encourage us to exploit its potential to the full.
Role of Interleukin 4 and Gamma Interferon in the Regulation of Human IgE Synthesis: Possible Alterations in Atopic Patients
Authors: Romagnani S. , Maggi E. , Del Prete G.F. , Parronchi P. , Macchia D. , Tiri A. , Ricci M.
Published: August 2009

The IgE helper function of human T cell clones or their phytohemagglutinin-induced supernatants was positively correlated with their ability to produce or their content in interleukin 4 (IL-4), whereas it was inversely correlated with production of or content in gamma interferon. The addition to B cell cultures of anti-IL-4 antibody abolished not only the IgE synthesis induced by recombinant human IL-4, but also that induced by IL-4-producing T cell clones or their phytohemagglutinin-induced supernatants. A clonal analysis in non-atopic donors and patients with common atopy showed that atopies possess in their peripheral blood significantly higher numbers of T cells able to secrete IL-4 and to provide helper function for IgE.
Isotype-Specific Suppression of IgE Synthesis in a Human Myeloma Cell Line (U-266) by an IgE-Binding Protein Derived from Normal Human Peripheral Blood Cells
Authors: Jernberg Helena , Nilsson Gunnar , Ahlstedt Staffan , Nilsson Kenneth
Published: August 2009

Human peripheral blood cells produce immunoglobulin-binding factors upon stimulation with purified protein derivative. The binding factors from 2 healthy individuals were purified by IgE affinity chromatography. IgE-suppressive activity was demonstrable using the IgE-producing human myeloma cell line U-266 as an assay system. The effect of the suppressive factor seems to be reversible, isotype specific, as the immunoglobulin synthesis in the IgGk-producing U-1958 myeloma line was not affected, and selective for the epsilon heavy chain. The results also suggest that this suppression is not the result of a decrase in DNA synthesis or suppression of protein synthesis in general.
Interleukin 4 Dependent Induction of IgE Synthesis and CD23 Expression by the Supernatants of a Human Helper T Cell Clone
Authors: Vercelli Donata , Leung Donald Y.M. , Jabara Haifa H. , Geha Raif S.
Published: August 2009

The supernatants of the human alloreactive helper T cell clone Al, which secretes interleukins (IL) 4 and 5, could induce IgE synthesis by normal peripheral blood mononuclear cells and expression of FcεR2/CD23 on normal human monocytes. Both effects were IL-4 dependent, since they could be induced by recombinant IL-4 alone and were inhibited by an anti-IL-4 antibody. The activation of such clones may contribute to the high IgE production and the high percentage of circulating CD23+ monocytes observed in allergic disorders.
Factors Influencing Basophilic Differentiation of HL-60 Cells
Authors: Denburg Judah A. , Hutt-Taylor Stephen , Dolovich Jerry , Switzer Jan , Harnish Delsworth G.
Published: August 2009

Lineage-specific hematopoietins apparently act in concert with multipotent factors in an orderly sequence of growth and differentiation. We have used the human acute promyelocytic leukemia cell line HL-60 to examine basophilic differentiation, using radioenzymatic assay of histamine content as an end point. Recombinant human interleukin 1 (rhIL-1), rhIL-2, rhIL-4, and recombinant human alpha and gamma interferons did not stimulate basophilic differentiation either in the presence or absence of sodium butyrate, an important cofactor for induction of differentiation. In contrast, rhG-CSF (granulocyte colony-stimulating factor), rhGM (granulocyte-macrophage) CSF, rhIL-3, rhIL-5, nerve growth factor, conditioned medium (CM) from the hairy T cell leukemic line Mo, and nasal polyp epithelial CM stimulated significant increases in histamine content in HL-60 cells at day 5 in vitro. GM-CSF did not account for all of the basophilic differentiating activity in Mo-CM. The data suggest that a unique, lineage-specific, basophilic cell differentiation factor is produced by T cells and point to the possible diagnostic and therapeutic relevance of in situ hematopoietic mechanisms in human respiratory disease.
Characteristics of Histamine Secretion Induced by Neuropeptides: Implications for the Relevance of Peptide-Mast Cell Interactions in Allergy and Inflammation
Authors: Pearce F.L. , Kassessinoff T.A. , Liu W.L.
Published: August 2009

A variety of basic, sensory neuropeptides induced the release of histamine from rat peritoneal mast cells. However, a wide range of other polycationic agents, such as compound 48/80, the mast-cell-degranulating peptide from bee venom and polylysine also activated this cell type. Histamine release induced by all of these agents had characteristic features in common. In each case, the process was extremely rapid, essentially independent of added calcium or phospholipids, not mediated through cell-fixed antibodies, and inhibited by antagonists of the so-called polyamine receptor. The release was also very species- and tissue-specific. All of the compounds were most active against rat serosal mast cells. Tissue mast cells of this species and peritoneal mast cells of other rodents showed graded responses while guinea pig and human mast cells were unreactive. On the basis of these results, the possible role of peptide-mast cell interactions in neurogenic models of inflammation is discussed.
Prostaglandin H Synthetase Activates Xenobiotics into Free Radicals: Histamine Release and Biochemical Characteristics
Authors: Masini Emanuela , Giannella Eliana , Palmerani Beatrice , Pistelli Alessandra , Gambassi Francesco , Mannaioni Pier Francesco
Published: August 2009

In isolated rat serosal mast cells, studies with the fluorescent Ca2+ indicator, quin 2, and with [3H]-myoinositol to label endogenous polyphosphoinositides have established that an increase in cytosol Ca2+ levels was obligatory for histamine release by free radicals. No substantial breakdown of phosphatidylinositol and related polyphosphoinositides was associated with generation of the Ca2+ signal and histamine release, suggesting that the release of histamine by free radicals entails different pathways than the calcium-mobilizing receptors linked to polyphosphoinositides as second messengers.
PAF-Acether and Experimental Anaphylaxis as a Model for Asthma
Authors: Pretolani Marina , Lellouch-Tubiana Arielle , Lefort Jean , Bachelet Marie , Vargaftig B. Boris
Published: August 2009

Several lines of evidence indicate that platelet-activating factor (PAF-acether) is implicated in hypersensitivity reactions. Indeed, PAF-acether reproduces the features of asthma in vivo and in vitro, since it induces bronchoconstriction, hypotension, and hemoconcentration and activates platelets and leukocytes. Both PAF-acether and antigen evoke eosinophil margination and diapedesis in guinea pig lung parenchyma and bronchial submucosa. Furthermore, intradermal administration of PAF-acether to atopies induces a more intense eosinophil degranulation as compared to normal subjects. PAF-acether also induces bronchopulmonary hyperresponsiveness in various animal models and in humans. We showed that lungs from actively sensitized guinea pigs exhibit an in vitro bronchopulmonary hyperresponsiveness to PAF-acether as compared to non-sensitized animals. This phenomenon is probably due to a lung invasion by inflammatory cells or to a variation of the reactivity of resident lung cells such as alveolar macrophages. In these cells, the cyclic adenosine mono-phosphate content is much less increased by prostaglandin E2 and salbutamol when they are obtained from actively sensitized animals.
Effect of Platelet-Activating Factor on Monocyte Activation and Production of Tumor Necrosis Factor
Authors: Bonavida B. , Mencia-Huerta J.-M. , Braquet P.
Published: August 2009

The effect of platelet-activating factor (PAF) or human peripheral-blood-derived monocytes (PBM) was examined. The addition of PAF to monocyte cultures did not activate the cells to mediate cytotoxicity activity against 51Cr-labeled target cells. Furthermore, supernatants derived from the treated cultures were not cytotoxic. However, these supernatants contained tumor necrosis factor (TNF) when assayed by a sensitive radioimmunoassay. Further kinetic studies indicated that cytotoxic supernatant is detected at 2–4 h following PAF treatment but not overnight treatment, suggesting, perhaps, the presence of inhibitors interfering with the cytotoxic activity. Cells pretreated with PAF responded poorly to a second stimulation with phorbol myristate acetate whereas a secondary response was seen with cells pretreated with interferon-γ. These results suggest that PAF is involved in regulating cytokine production by monocytes and thus plays a role in the immune response to foreign antigens.
Effect of Long-Term Treatment with Platelet-Activating Factor on Cytokine Production by Rat Spleen Cells
Authors: Pignol Bernadette , Hénane Sylvie , Mencia-Huerta Jean-Michel , Braquet Pierre
Published: August 2009

The long-term in vivo effect of platelet-activating factor (PAF) production of interleukin-1 and -2 (IL-1, IL-2) was investigated. Alzet infusion minipumps loaded with PAF or solvent were placed under the back skin of Sprague-Dawley rats and connected to the jugular vein. Lymphocytes from animals having received 1, 4.5 or 9 μg PAF/7 days showed an increased capacity to produce IL-1 and IL-2. In contrast, splenocytes from rats receiving 28 μg PAF/7 days exhibited decreased capacity to produce IL-1, whereas IL-2 was unaffected. The decrease in IL-1 synthesis induced by 28 μg PAF and the increase in IL-2 production evoked by 1 μg PAF were not observed in rats treated daily with the PAF antagonist, BN 52021. Thus, PAF appears to play a role in the regulation of the immune response. The reversal of the effect of PAF by BN 52021 indicates that the mediator is acting via specific binding sites similar to those reported on other cell types. These data also suggest that PAF antagonists may be used as immunomodulatory drugs.
Clonal Analysis of the Cellular Immune Response to the House Dust Mite Dermatophagoides farinae
Authors: O’Hehir Robyn , Young Douglas , Kay Barry , Lamb Jonathan
Published: August 2009

A panel of human CD4+ T cell clones specific for the house dust mite was isolated from an atopic individual with perennial rhinitis. Soluble antigen specificity was defined using proliferation assays and subsequently the antigenic determinants recognized by some of these clones were mapped using nitrocellulose immunoblots of fractionated Dermatophagoides spp. Both cross-reactive and species-specific T cell clones were identified and in some instances their specificity could be mapped to the serologically defined Der f l, Der p I and Der f II allergens. In comparison, the serum antibody response showed additional specificity for Der f lll. The antigen recognition by six of these clones was found to be restricted by HLA-DR gene products.
Allergens of the House Dust Mite Dermatophagoides farinae. II. Immunological Characterization of Four Allergenic Molecules
Authors: Yamashita Naomi , Haida Michiko , Suko Matsunobu , Okudaira Hirokazu , Miyamoto Terumasa
Published: August 2009

In a previous study, we detected four major allergens from the house dust mite extract prepared from the body of Dermatophagoides farinae, employing radioimmunoelectrophoresis. The four allergenic proteins were designated as Me1, Me2, Me3 and Me4. The most prevalent allergen was found to be Me1 and its molecular weight was determined to be 17,000 daltons. In this study, the molecular weight of the second prevalent allergen, Me2, was determined to be 27,000 daltons using the immunoblotting method. The molecular weights of the other two major allergens, Me3 and Me4, were also estimated.
Age-Dependent Changes of Isotype and Idiotype Expression in the Antibody Response to the Phosphorylcholine Hapten in BALB/c Mice
Authors: Gerber V. , Ponnappan U. , Heusser C.H. , Cinader B. , Blaser K.
Published: August 2009

The distribution of antibodies among different isotypes in an immune response to a given antigen reflects the immunoregulatory linkage of T and B cell compartments, the genetic background of an individual and the functional state of its immune system. In addition, idiotypes are markers for the clonal origin of antibodies and their genetic relationship. Therefore, we have analyzed the isotype patterns and development of the major idiotype (T15) in BALB/c mice of different ages, immunized with a T-cell-dependent phosphorylcholine conjugate. The response was dominated by µ, γ3 and γ1 isotypes. The proportion of these antibodies changed in the progress of immunization but not with age in the primary response. An age-dependent change of the isotype distribution was observed only in the memory response. The T15 idiotype was dominantly expressed in the primary response and decreased in the memory response by 80–95% independently of the age of the mice. The results demonstrate that 2 populations of anti-phosphorylcholine antibodies which both prefer particular isotypes are expressed according to the functional state of the T and B cell compartments with age.