bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural Cell-Derived Cytokines in Allergic Inflammation
Authors: Denburg Judah A. , Gauldie Jack , Dolovich Jerry , Ohtoshi Takayuki , Cox Gerard , Jordana Manel
Published: August 2009

Based on observations of fluctuations in progenitors for inflammatory cells during allergic responses, we have proposed that a primary determinant of allergic inflammation involves microenvironmental influences on hemopoietic cell differentiation and phenotype; in addition, as a corollary of this, inflammatory cell burden is proposed as an important indicator of the severity and pattern of the inflammatory process in allergy. The studies outlined here focus on the effects of epithelial-cell- and fibroblast-derived cytokines on granulocytic and monocytic cell differentiation and activation in models involving allergic reactions in the upper and lower airways. Pure cultures of nasal or bronchial epithelial cells or fibroblasts are observed to give rise to cytokines important in inducing the differentiation of basophils, eosinophils, neutrophils and monocyte/macrophages. Gene expression, production and secretion of granulocyte/macrophage-colony-stimulating factor, interleukin-6 (IL-6) and IL-8 can be demonstrated in vitro and in vivo. Up-regulation of gene expression and production of these cytokines, which are important in inducing basophil, eosinophil and neutrophil/macrophage differentiation in several assays, is seen with IL-1 and the neuropeptide substance P; conversely, inhibition of cytokine production by structural cells is observed after pretreatment with corticosteroids in vitro, paralleling in vivo effects. Other modulatory effects also examined include: antiallergic compounds, which may affect posttranscriptional events in cytokine production, and heavy metal ions, which can also induce changes in gene expression. Structural-cell-derived extracellular matrices appear also to be important both in mast cell differentiation and in macrophage cytokine gene expression, both of which potentially feedback upon chronic allergic inflammatory processes, leading to their perpetuation. On the basis of these studies, it is proposed that microenvironmental controls of the inflammatory process involve the initiation and perpetuation of allergic inflammation through effects on cell differentiation by altered structural cells resident in the tissue. In vivo models to directly test this hypothesis are currently under exploration.
Production of Interleukin-4 and Other Cytokines following Stimulation of Mast Cell Lines and in vivo Mast Cells/Basophils
Authors: Seder Robert A. , Paul William E. , Ben-Sasson Zami , LeGros Graham S. , Kagey-Sobotka Anne , Finkelman Fred D. , Pierce Jacalyn H. , Plaut Marshall
Published: August 2009

Interleukin-3 (IL-3)-dependent mast cell lines, upon stimulation by calcium ionophores or by FcεRI cross-linking, express mRNA for, and secrete, a distinct pattern of cytokines, similar to those secreted by cloned mouse T cells of the TH2 type. The mast-cell-derived cytokines include IL-3, IL-4, IL-5 and IL-6. Not only in vitro mast cell lines, but also in vivo derived peritoneal mast cells secrete cytokines. An in vivo derived cell, in mouse spleen and bone marrow, secretes IL-4 and other cytokines upon stimulation with calcium ionophores or by FcεRI cross-linking or FcγRII cross-linking. The IL-4-producing cells are highly enriched in the FcεR+ subset of spleen and bone marrow cells. These FcεR+ cells produce large amounts of IL-4, and they have characteristics similar to those of immature mast cells and/or basophils. It is possible that cytokines produced by mast cells and/or basophils participate in allergic inflammatory diseases.
Histamine-Releasing Factors
Authors: Kaplan Allen P. , Baeza Maria , Reddigari Sesha , Kuna Piotr
Published: August 2009

Histamine-releasing factors (HRF) are cell-derived products which cause histamine release from basophils and/or mast cells. We have isolated HRF from human mononuclear cells and platelets and have purified 3 molecular species having molecular weights of 8–10, 15–17 and 35–41 kilodaltons (kDa). We prepared monoclonal antibodies to the 8- to 10-kDa form and have isolated it by affinity chromatography. A broad band was seen upon sodium dodecyl sulfate gel electrophoresis in 15% gels as well as immunoblotting, and the band was divided into an upper and a lower half. Amino acid sequence analysis of the upper half indicated that it is closely homologous to connective-tissue activating peptide III (CTAP III). The lower half also aligned with CTAP III beginning with amino acid 16; thus, proteolysis had occured removing the N-terminal 15 amino acids. This corresponds to neutrophil-activating peptide 2. Both appear to be active on basophils with a dose-response between 250 ng up to 10 μg. Although interleukin-3 and granulocyte/macrophage-colony-stimulating factor have similar histamine-releasing capability at lower effective concentrations, they do not account for HRF activity in mononuclear cell/platelet supernatants, and the 15- to 17 and 40- to 41-kDa moieties appear to be unique gene products unrelated to previously described cytokines.
The Characteristics of Antigen Define the Cellular Source and Kinetics of Histamine-Releasing Factor Induced by Human Peripheral-Blood Mononuclear Cells
Authors: Turner K.J. , Strickland D. , Siemensma N.P. , Holt B.J.
Published: August 2009

Peripheral-blood leucocytes from Dermatophagoides pteronyssinus- and/or Lolium perenne-allergic patients produce in vitro histamine-releasing factor (HRF) in an allergen-specific and concentration-dependent relationship. Maximum production of HRF occurred in cultures containing as little as 10–100 pg/ml crude allergen extract, although a second peak occurred at higher concentrations (10–100 μg/ml). While HRF was detectable in 1-hour cultures, maximal production required 24 h in culture. In contrast, HRF induced by streptokinase/streptodornase (SK/SD) was generally maximal after 1 h. Allergen-induced HRF production was almost exclusively associated with monocytes and B cells. In contrast, peripheral-blood T cells were the major source of induced HRF production in cultures containing SK/SD. Histamine-releasing cytokines are apparently produced by different cell populations, the activation of which may be dependent upon the characteristics of the stimulating antigen.
Regulation of Mediator Release by Human Basophils: Importance of the Sequence and Time of Addition in the Combined Action of Different Agonists
Authors: Dahinden Clemens A. , Bischoff Stephan C. , Brunner Thomas , Krieger Martin , Takafuji Shigeru , de Weck Alain L.
Published: August 2009

Biologically active molecules affecting basophil function can be divided into 4 groups according to their capacity to induce basophil degranulation and/or leukotriene generation: (1) full agonists such as anti-IgE or fMLP, which induce both histamine and leukotriene release; (2) partial agonists such as C5a, which induces degranulation only; (3) incomplete agonists such as neutrophil-activating peptide-1, platelet-activating factor or C3a, which induce mediator release only after cytokine preincubation, and (4) basophil response modifiers, such as interleukin-3, interleukin-5 and granulocyte/macrophage-colony-stimulating factor, which (a) enhance the releasability to all basophil agonists, (b) change the mediator profile, (c) enhance the rate of mediator release, (d) render basophils responsive to lower agonist concentrations and (e) render basophils responsive to incomplete agonists. We demonstrated that histamine release and de novo synthesis of lipid mediators are clearly separately regulated, and that combined actions of different molecules are of importance. In particular, the type(s), the time interval and the sequence of action of basophil-activating molecules are crucial for the final outcome of the basophil release reaction.
Identification of a Spleen Cell-Derived Factor that Inhibits Sensitization of Murine Peritoneal Mast Cells as Interferon-Gamma
Authors: Coleman J.W. , Morris A.G.
Published: August 2009

We present evidence that a spleen cell-derived factor that inhibits the sensitization of mouse peritoneal mast cells is IFNγ. Conditioned medium (CM) from Con A-activated mouse spleen cells and recombinant MuIFNγ both inhibited antigen-induced 5-HT release from peritoneal mast cells when added at the sensitization stage, but were without effect on presensitized cells. Both preparations were active at dilutions corresponding to similar levels of IFN activity (1–10 units/ml). The inhibitory activity of CM was blocked by a rat monoclonal MuIFNγ-neutralizing antibody, thus confirming that IFNγ was the active molecule.
Interleukin-4 Gene Expression and IgE Responsiveness
Authors: Okudaira Hirokazu , Mori Akio , Akiyoshi Kazuhiko , Yamamoto Kazuhiko , Suko Matsunobu , Watanabe Naohiro , Ito Mamoru , Takahashi Koki , Juji Takeo
Published: August 2009

Interleukin-4 (IL-4) gene expression by stimulation with concanavalin A (Con A) in murine spleen cells was examined. The amount of IL-4 mRNA induced by Con A was greatest in spleen cells obtained from IgE high responder strains of mice. A trace amount of IL-4 mRNA was induced in spleen cells from IgE low responder (SJL) mice. The amount of IL-4 mRNA induced in spleen cells from an IgE intermediate responder (C57BL/6) was smaller than that from high responders, but significantly greater than that from low responders. Spleen cells from IgE nonresponders (SJA/9) developed only a negligible amount of IL-4 mRNA. IL-4 mRNA was detected in human peripheral blood mononuclear cells (PBMC) stimulated with Con A. The IL-4 gene expression seemed to be greater in PBMC obtained from highly atopic patients and was decreased in PBMC from individuals showing hypo-IgE immunoglobulinemia (less than 10 IU/ml). The results obtained in the present study may indicate that high and low IgE responder traits are determined depending on their levels of IL-4 mRNA expression.
Functional Heterogeneity of Human Mast Cells
Authors: Pearce F.L. , Boulos P.B. , Lau H.Y.A. , Liu W.L. , Tainsh K.R.
Published: August 2009

Mast cell heterogeneity in man is much less sharply defined than in the rodent but human cutaneous mast cells appear to be distinct in their histochemical properties, their reactivity to polycationic histamine liberators, and their relative lack of responsiveness to antiasthmatic chromones.
Allergenicity and Physicochemical Characterization of House Dust Mite Derived Amylase
Authors: Lake Fiona R. , Ward Larry D. , Simpson Richard J. , Thompson Philip J. , Stewart Geoffrey A.
Published: August 2009

The enzyme amylase was shown to be present in extracts prepared from both house dust and spent growth medium used in the culture of the mite Dermatophagoides pteronyssinus. In dust, it was shown to correlate with both mite counts and concentrations of the faecally derived mite allergen, Der p I. Mite amylase was isolated from the culture medium and shown to be a single chain protein with a molecular weight of 56,000. The enzyme contained free sulphydryl groups and had the N-terminal sequence, KYXNPHFIGX-RSVITXLME. It was found to be an allergen using sera from adults (46% positive) and children (25%) who were mite allergic. The expression of allergenicity was dependent on the integrity of intra-chain disulphide bonds.
A Low Molecular Weight Allergen of White Birch (Betula verrucosa) Is Highly Homologous to Human Profilin
Authors: Valenta Rudolf , Duchêne Michael , Breitenbach Michael , Pettenburger Karin , Koller Lore , Rumpold Helmut , Scheiner Otto , Kraft Dietrich
Published: August 2009

Cloning of allergens has contributed substantially to the understanding of mechanisms in allergic diseases by providing information about the sequence and hence biological functions of allergens. The major birch pollen allergen, Bet v I [Breiteneder H, et al: EMBO J 1989;8:1935–1938] and the white-faced hornet venom allergen (antigen 5) [Si Yun Fang K, et al: Proc. Natl. Acad. Sc. USA 1988;85:895–899] were shown to be highly homologous to pathogenesis-related proteins of plants. In the case of the major allergen of house dust mite, Der p I, homology to proteases was demonstrated. Therefore, the proposed biological function of these IgE-binding proteins might be related to their allergenic potential. In this paper we tentatively identify a ubiquitous family of low molecular weight allergens as profilins. The identification is based on a sequence homology, (b) binding to poly(L-proline), and (c) immunological cross-reactivity. Recombinant birch profilin was purified to homogeneity and showed the same properties as natural profilins.
Investigation of House Dust Mite (Dermatophagoides pteronyssinus) Allergen Extracts Prepared from Purified Mite Bodies and Whole Mite Culture
Authors: Wahl R. , Weber B.F.
Published: August 2009

Allergen extracts prepared from purified mite bodies (PMB) and whole mite culture (WMC) were investigated by using in vivo and in vitro methods. PMB showed a more complex allergen pattern than WMC. In PMB, 6 out of 16 allergens could be detected as major allergens. In WMC, 5 out of 10 allergens could be detected as major allergens. Both extracts contained the same amount of the major allergen Der p I. By skin prick testing comparable results were obtained with both extracts. Investigation of the reproducibility showed that 15 production lots of PMB could be produced in a high conformity according to their allergenic potency and their protein and allergen composition.
Elucidation of the Epitope Locations of Human Autoanti-IgE: Recognition of Two Epitopes Located within the Cε2 and the Cε4 Domains
Authors: Shakib F. , Powell-Richards A.
Published: August 2009

IgG autoanti-IgE is detectable in a large proportion of individuals with allergic asthma, where it is suggested to be potentially involved in modulating IgE-mediated hypersensitivity. Using a series of overlapping recombinant human ε-chain peptides, we have shown that circulating IgG anti-IgE antibodies recognise at least 2 epitopes located within the Cε2 and the Cε4 domains, respectively. The Cε2 recognition site is located within the C-terminal portion of the Cε2 domain (i.e. aa301–339) which is thought to contribute residues to the FcεRI-binding site on IgE. The recognition by autoanti-IgE of an effector function site of such pivotal importance in IgE-mediated hypersensitivity suggests that it plays a possible modulatory role during mast cell and basophil activation.
The Immune Response to Anti-Idiotype Antibodies Bearing an Internal Image Epitope of Tetanus Toxin/Toxoid
Authors: Poskitt D.C. , Turnbull S. , Macdonald L. , Jean-François M.J.B. , Yasmeen D.
Published: August 2009

Primary immune responses to tetanus toxoid (TT) and primary and secondary immune responses to a rabbit TT internal image bearing anti-idiotype antibody (Ab2β1) inoculated in Freund’s complete adjuvant (FCA), saline (SAL) or syntex adjuvant formulation vehicle (SAF) via the intraperitoneal or subcutaneous route, were examined in mice. High anti-TT antibody (Ab3) titres are reported although the titre and persistence of the antibody response varied according to the adjuvant used in the priming and challenge inocula of Ab2β1. Mouse Ab3 antibodies were elicited in mice inoculated with rabbit Ab2β1 antibodies which in turn were elicited by an inoculum of mouse monoclonal anti-TT Ab1 antibody. Ab3 was shown to be identical to Ab1 by immunoblot analysis. Primary and secondary immune responses elicited by rabbit Ab2β1 antibody protected mice against a lethal dose of tetanus toxin.
Experimental Allergic Encephalomyelitis – Prophylactic and Therapeutic Treatment with the Cyclooxygenase Inhibitor Piroxicam (Feldene®)
Authors: Weber Frank , Meyermann Richard , Hempel Klaus
Published: August 2009

Prophylactic administration of Piroxicam (Feldene®), a reversible inhibitor of prostaglandin biosynthesis, significantly reduced the occurrence of paralytic signs and the amount of antibodies against myelin basic protein in the model of mild acute experimental allergic encephalomyelitis in the Lewis rat. Mononuclear infiltration of the central nervous system remained unaffected. A therapeutic intervention with piroxicam, however, increased paresis and CNS pathology. Immunohistochemical studies revealed an increased proportion of ED1-positive macrophages and monocytes in the infiltrates of the spinal cord in animals treated with piroxicam. Possible reasons for the different effects of the prophylactic and therapeutic treatment are discussed in the study.
Histamine Stimulation of the Nasal Mucosa Does Not Induce Prostaglandin or Leukotriene Generation or Induce Methacholine Hyperresponsiveness
Authors: Majchel Abraham M. , Proud David , Hubbard Walter C. , Naclerio Robert M.
Published: August 2009

To further define the role of histamine in the nasal mucosa, we studied the possible effect of histamine provocation on the generation of prostanoids and leukotrienes, and on the induction of hyperresponsiveness to methacholine. In separate experiments, we performed nasal challenges with histamine and measured by gas chromatography negative ion mass spectrometry and by radioimmunoassay after high-performance liquid chromatography the levels of prostanoids and leukotrienes, respectively, in recovered nasal lavages 10 min after challenge. Hyperresponsiveness to methacholine was tested in both nostrils 24 h after unilateral provocation with histamine. Our data suggest that histamine induced an immediate symptomatic response, but neither led to the generation of prostaglandins or leukotrienes nor induced hyperresponsiveness to methacholine. These results differ from those achieved after antigen stimulation and emphasize the importance of mediators in addition to histamine in the allergic reaction.
Effect of a Fish Oil Diet on Asthma: Results of a 1-Year Double-Blind Study
Authors: Dry J. , Vincent D.
Published: August 2009

Airway inflammation is a major component of asthma. Food intake of N-3 fatty acids (FA) is associated with a low incidence of inflammatory diseases, such as asthma. We treated 12 asthmatic patients with FA and report the positive results of this 1-year double-blind study. A positive effect on forced expiratory volume in 1 s was observed after the 9 month of treatment. Our results are in favor of the use of FA, but have to be confirmed by other studies.
Stimulation of Human Peripheral Blood Lymphocytes with Chironomid Hemoglobin Allergen (Chi t I)
Authors: Liebers V. , Schalbaba S. , Mazur G. , Baur X.
Published: August 2009

Hemoglobins (Chi t I) of the dipteron species Chironomus thummi thummi are known to cause severe allergic diseases in humans. We tested the allergen-specific stimulation of human peripheral blood lymphocytes (PBL) by Chi t I and its nine main components. Further, we applied fragments of the well-analyzed component III, obtained by cleavage with trypsin as well as arginine protease. In this way, we screened the molecule in order to identify T-cell epitopes. The whole component was found to be immunogenic and to have regions demonstrating varying PBL stimulation. In addition, interindividual patterns of reactivity, probably due to genetic restriction, were found. A T-cell epitope could be shown to be within the site 98–111, as predicted by application of Rothbard’s algorithms.
Immunoregulation of Endometrial and Jejunal Epithelia Sensitized by Infection
Authors: Castro Gilbert A. , Harari Yael
Published: August 2009

The hypothesis was tested that the uterus of the rat orally infected with the parasite Trichinella spiralis becomes hypersensitized and that subsequent antigenic challenge affects functions in the endometrial epithelium. Results of experiments comparing the immunological responsiveness of isolated rat uterus with that of the jejunum supports our hypothesis. Antigenic challenge of uterus mounted in Ussing-type chambers causes an elevation in transuterine short circuit current (Isc) of 6.4 ± 0.8 μA/cm2. The transduction of the antigenic signal to elicit the electrophysiological response involves 5-hydroxytryptamine (5-HT) working through a nerve-independent pathway. The antigen-stimulated rise in Isc peaks ∼3 min after challenge. The uterine response is blocked by diisothiocyanostilbene-2,2′-disulfonic acid, an inhibitor of bicarbonate-chloride exchange. The antigen-evoked change in jejunal Isc is biphasic, peaking at 1.5 and ∼4.0 min after challenge, and is about 10-fold greater in magnitude than the Isc in the uterus. The transductive pathway in the jejunum involves 5-HT, histamine and prostaglandin acting partly through intrinsic nerves. The jejunal response to antigen is inhibited by diphenylamine-2-carboxylate, a chloride channel blocker. Changes in net ion transport which are primed by infection and evoked by antigen are apparently triggered by local anaphylaxis in both the uterus and jejunum.
Appearance of Macrophage Migration Inhibition Factor in Patients with Systemic Reactions to Bee Venom
Authors: Goldberg Arnon , Livni Ella , Mekori Yoseph A.
Published: August 2009

Cellular responses in bee venom (BV) allergy is a controversial issue. Previous studies could not reach an agreement whether this mechanism is activated as a result of allergic sensitization to bee venom. All previous works have used lymphocyte proliferation as their method to analyze cell-mediated immunity. In the present work, we tried to explore whether the production of macrophage migration inhibition factor (MIF), which is another in vitro correlate with cellular responses, is increased in these patients. We also examined which of the major antigenic components of BV played a significant role in the cellular response. Peripheral blood lymphocytes from 10 patients with systemic allergic reactions to bee sting and 9 healthy volunteers were examined for their ability to induce positive MIF reponses. Macrophage inhibition was significantly increased in allergic patients when tested with BV, phospholipase A2 (PLA2) and with melittin. Positive MIF responses to other components were also more common in allergic patients than in the control group. Our results indicate that cellular response to BV is expressed in patients with systemic allergic reaction to BV. When major antigenic components of BV are examined, PLA2 seems to play the major role in inducing this response.
Antigen Dose-Dependent Regulation of Bε-Memory Cell Expression
Authors: Kolbe Ludger , Heusser Christoph , Kölsch Eckehart
Published: August 2009

The data presented in this study document that the phospholipase A2 (PLA2)-specific IgE antibody response in high responder CBA/J mice is solely dependent on the antigen dose used for immunization. Repeated injections of minute doses (MD) of antigen (0.1 μg/mouse) induce a persisting high level of PLA2-specific IgE antibody titer, whereas large doses (LD) (10 μg/mouse) induce a persisting low level of IgE. The IgG antibody titers are the same under both conditions. The low level IgE immune status induced by repeated LD is irreversible and cannot be boosted by MD. In contrast a single LD primes for a secondary IgE response which can be recalled by MD. A high level of PLA2-specific IgE antibodies induced by MD can be downregulated by a single intervening LD of antigen. A low level IgE immune status can be transferred with spleen cells of mice immunized with LD into naive syngeneic recipients, which then fail to mount a high level IgE response upon injection of MD of antigen. The experiments reveal two countercurrent processes, induction of Bε-memory cells after a single LD and additional activation of a persisting IgE-specific cellular suppression mechanism after repeated LD of antigen. These properties make the system suitable for the analysis of cellular interactions and of potential desensitization protocols.
Defective Lectin-Induced p55kDa-IL2R Expression on Peripheral T Cells in Non-Hodgkin’s Lymphoma Patients
Authors: Hiroishi Keisai , Nakanishi Kenji , Yoshimoto Tomohiro , Hada Toshikazu , Higashino Kazuya
Published: August 2009

We examined 19 non-Hodgkin’s lymphoma patients for their responsiveness to lectin stimulation, as measured by T cell proliferative response and p55kDa-IL2R expression. Our results indicate that both these responses were remarkably depressed in non-Hodgkin’s lymphoma patients and the deficiency of lectin-induced p55kDa-IL2R expression correlated closely with the reductions in the lectin-induced T cell proliferative responses. The evidence that costimulation with PMA can partially overcome the IL2R defect might allow us to localize the cellular defects and rationally design chemotherapeutic agents corrective for these patients’ poor p55kDa-IL2R inducibility.
Allergic Hepatitis in Guinea Pigs Induced by 2,4,6-Trinitrophenyl Liver Protein Conjugate
Authors: Nishimoto Hirofumi , Mori Koh-ichi , Mizoguchi Yasuhiro
Published: August 2009

Experimental drug-induced allergic hepatitis was induced in guinea pigs which had been immunized to the 2,4,6-trinitrophenyl (TNP)-conjugated liver protein first peak (TNP-LP1) emulsified in complete Freund’s adjuvant (CFA). Delayed-type hypersensitivity (DTH) was elicited in the immunized animals by intradermal challenge with TNP-LP1. When TNP-LP1 was introduced into the liver via the mesenteric vein, allergic hepatitis was provoked. Histological examination of the liver revealed massive monocytic infiltration and focal hepatic necrosis in the periportal areas. Blood biochemical analysis showed increased levels of glutamate oxalacetate transaminase (GOT) and total bilirubin. TNP-modified hepatocytes were found to be effective as a challenge elicitor to the immunized animals to induce both DTH skin reaction and allergic hepatitis. In the latter case, the severity of the lesion was stronger than that observed by the challenge with TNP-LP1.
Survey of Hanganutziu and Deicher Antibodies in Operated Patients
Authors: Higashihara Tomoko , Takeshima Toshio , Anzai Mitsuaki , Tomioka Minetoshi , Matsumoto Kaoru , Nishida Katsunori , Kitamura Yoshio , Okinaga Kota , Naiki Masaharu
Published: August 2009

The appearance of Hanganutziu and Deicher (HD) antibody in the sera of patients suffering from various diseases, including malignancies of some organs and liver disorders, was investigated by enzyme-linked immunosorbent assay using N-glycolylneuraminyl-lactosylceramide (HD3) and 4-O-acetyl-HD3 as the antigenic molecules. More than 25% of sera from patients suffering from malignancies, cholelithiasis and liver cirrhosis had HD antibody, whereas none of 41 sera from healthy persons had HD antibody. The percentage of HD antibody-positive patients was similar in stages I, II and III of gastric cancer and recurrence cases. Antibody titers of the positive patients in each stage were also not different from those in each other stage. These results indicated that HD antigenic expression on cancerous tissue is not dependent on the cancerous malignancy. The HD antibody level was elevated after surgical removal of cancerous tissues in 5 of 6 patients examined, indicating that tumor growth absorbed the serum antibody. Serum antibody against 4-O-acetyl-HD3 was detected independently of HD3 antibody in some cases; however, in most cases, correlation between the two antibody titers was observed.
Lysosomal Enzyme Activities in Experimental Granulomatous Inflammation
Authors: Kaga Shuji , Kobayashi Kazuo , Yamagata Noriko , Takeuchi Hiroko T. , Yoshida Kazue , Matsuda Tomoko , Nakatani Kazuko , Kasama Tsuyoshi , Kasahara Keita , Takahashi Terumi
Published: August 2009

Foreign-body (dextran beads) and hypersensitivity (antigen-coupled agarose beads) lung granulomas were induced in BALB/c mice by the intratracheal injection of beads. Large granulomas developed, which reached peak intensity within 3 days and declined in size thereafter. Aqueous extracts of both granulomas contained high levels of lysosomal enzymes N-acetyl-β-D-glucosaminidase (NAG) and lysozyme. Lysosomal enzyme activities in the extracts correlated with granuloma sizes. Dispersed granuloma cells were able to produce these enzymes. These results suggest that lysosomal enzymes may reflect the activity/size of granulomatous inflammation.
Interleukin-4-Induced IgG Subclass and IgE Secretion by Mononuclear Cells from Atopic Donors
Authors: Nüsslein Hubert G. , Winter Matthias , Träg Thomas , Kalden Joachim R.
Published: August 2009

To investigate the effect of interleukin-4 (IL-4) on the secretion of IgG subclasses and IgE in atopic individuals, peripheral blood mononuclear cells from 10 atopic and 10 normal donors were incubated with IL-4, and the production of IgE, IgG1, IgG2, IgG3, and IgG4 was determined after a 14-day culture period. Like normal peripheral blood mononuclear cells, atopic mononuclear cells were stimulated by IL-4 to secrete IgE and IgG4, but not the other IgG subclasses. This response was in the same quantitative ranges in both donor groups. Addition of interferon gamma to IL-4-containing cultures efficiently antagonized the IL-4-induced IgE and IgG4 secretion. These results do not support the hypothesis that an atopic condition is due to a discordant effect of IL-4 on IgE compared to IgG4 production or to an altered response to the potent antagonist interferon gamma.
Comparative Antigen Analysis of Different Life Stages of Schistosoma mansoni by Crossed Immunoelectrophoresis
Authors: Akhiani A.A. , Nilsson L.-Å. , Ouchterlony Ö.
Published: August 2009

Two-dimensional (crossed) immunoelectrophoresis was used for analysis of soluble antigen extracts obtained from the three developmental stages, cercariae, adult worms and eggs, of Schistosoma mansoni by using homologous hyperimmune sera produced in sheep. The antigenic relationships between the three stages as well as the possible relationship to the intermediate snail host were studied. Seven antigen components were shown to be shared between all three life stages of S. mansoni. Furthermore, one antigen was common to adult worm and snail, and one other antigen was shared between cercaria and snail. By using an intermediate gel containing lectin in the antigen-antibody system or by enzyme staining of the immune precipitates it was possible to identify schistosome antigens possessing lectin reactivity or enzyme activity. Characterization of enzyme activities revealed three individual precipitating antigens in adult worm of S. mansoni possessing esterase, leucyl-glycyl-glycine peptidase and phenylalanyl-leucine peptidase activities, respectively. One further precipitinogen with malate dehydrogenase activity was identified for all three life stages.
Interleukin-4 Gene Expression in Human Peripheral Blood Mononuclear Cells
Authors: Mori Akio , Yamamoto Kazuhiko , Dohi Makoto , Suko Matsunobu , Okudaira Hirokazu
Published: August 2009

Interleukin-4 (IL-4) mRNA was detected in normal human peripheral blood mononuclear cells (PBMC) stimulated with concanavalin A by Northern blot analysis. The signal was undetectable in PBMC before the stimulation, but became detectable 3 hrs after the stimulation and reached a maximum in 3–6 h and disappeared gradually thereafter. Immunosuppressive drugs such as ciclosporin, hydrocortisone and prednisolone inhibited the IL-4 mRNA expression dose dependently. Interferon-γ did not show any inhibitory effect on IL-4 gene expression.
Serum Antibody Responses in Mice to Intermittent Inhalation of Ovalbumin Dust
Authors: Gilmour M.I. , Wathes C.M. , Taylor F.G.R.
Published: August 2009

Serum antibody production and induction of antibody tolerance were monitored in mice following intermittent inhalation of ovalbumin dust (mass concentration = 4.2 mg m––3; diameter of 80% of particles < 2.6 μm). Repeated inhalation of microgram quantities of dust stimulated serum antibody production and development of tolerance. The sequence of these responses is analogous to that following oral presentation of antigen, but is produced by a much lower dose when antigen is presented via the respiratory tract.
IgG4 Autoantibodies to DNA in Systemic Lupus erythematosus Patients
Authors: Nagpal Sunil , Namboodiri M.S.A. , Subba Rao B.S. , Subba Rao P.V.
Published: August 2009

The presence of DNA-specific IgG4 antibodies was demonstrated in the sera of patients with systemic lupus erythematosus (SLE) by a microtiter solid-phase radioimmunoassay. A patient with distal inter-phalangeal swelling and extensive ulcers in the oral cavity, seronegative for anti-DNA antibodies of the IgG isotype, was found to have anti-DNA autoantibodies exclusively of the IgG4 subclass. These autoantibodies directed against the dsDNA conformation cross-reacted with chondroitin sulfate, dermatan sulfate and heparin.
Differences in Level and Avidity of Secretory IgA Antibodies in Breast Milk of Swedish, Indian and Japanese Mothers to Soybean Protein
Authors: Morikawa A. , Dahlgren U. , Carlsson B. , Narayanan I. , Hahn-Zoric M. , Hanson L.Å. , Maeda S. , Tomizawa S. , Kuroume T.
Published: August 2009

Colostrum was collected from Swedish, Indian and Japanese mothers. The samples were as a mean, collected 4.00–4.25 days after delivery of term infants. The level of specific IgA antibody to 2S, 7S and crude soybean antigen were measured by the enzyme-linked immunosorbent assay (ELISA). The avidity of the IgA antibodies to 7S soybean antigen was also measured with an ELISA system using different molarities of potassium thiocyanate for elution of the specific IgA antibody from solid phase-bound antigen. The level of specific IgA antibody to 7S and crude soybean antigen in the milk of the Indian mothers was significantly higher than in the milk of the Japanese mothers (p ≤ 0.01). In contrast, the avidity expressed as the molarity of KSCN for 50% elution of IgA antibody to 7S soybean antigen in the milk of the Japanese mothers was significantly higher than in the milk of the Indian mothers (p < 0.01).
Depolarizing Action of Allergens on Passive Sensitized Lymphocytes
Authors: Kosnikov V.V. , Dobretsov G.E.
Published: August 2009

An ability of rat thymus lymphocytes to respond to pollen allergens has been found. The lymphocytes were exposed with plasma of pollinosis patients. The subsequent addition of allergens specific for the patient caused the decrease of lymphocyte plasma membrane potential. The decrease was detected by use of potential-sensitive fluorescent probe 4-(p-dimethylaminostyryl)-1-methylpyridinium. This newly found effect can be employed for diagnostics of atopic states.
Identification of Soybean Proteins Responsible for Respiratory Allergies
Authors: González Rosa , Zapatero Lydia , Caravaca Francisco , Carreira José
Published: August 2009

Serum samples from 32 patients who suffered attacks during the asthma outbreaks of 1987 and 1988 in Cartagena, Spain, supposedly caused by soybean dust, were studied. At least 90% had specific IgE to shell components and only 13% showed specific IgE to shell-depleted soybean grains. A control group of 32 patients who also suffered asthma attacks but on different days from those of the outbreaks were negative. The shell’s most important allergen with an apparent molecular weight of 8 kDa was not present in shell-depleted grains. This allergen as well as other less important shell allergens may be different from the allergens already identified by using serum from patients suffering food allergy to soya.
Peripheral Denervation Suppresses the Late Phase of Delayed-Type Hypersensitivity
Authors: Josefsson Elisabet , Carlsten Hans , Lange Stefan , Tarkowski Andrej
Published: August 2009

The impact of peripheral denervation on antigen-specific immune responses was analysed on the B and T cell levels. Delayed-type hypersensitivity (DTH) response to sheep red blood cells (SRBC) or oxazolone was used in mice as a model system of in vivo T cell reactivity. Serum antibody levels to SRBC, measured by an enzyme-linked immunosorbent assay (ELISA), were evaluated to analyse the B cell response. The effect of peripheral denervation on immune responsiveness was studied both at the point of sensitisation and elicitation. The results show that peripheral denervation significantly suppresses the local DTH response. The late, inflammatory phase but not the early phase of the DTH reaction was reduced after denervation (p < 0.01). The DTH suppression by denervation was similar irrespective of whether the neurectomy was performed 1 or 4 weeks prior to sensitisation. Even in the contralateral limb, with intact innervation, the inflammatory DTH reactivity was decreased. We believe that this phenomenon might be due to abrogation of the reflex arch since the denervation procedure did not give rise to a significant systemic downregulation of DTH. Also, peripheral denervation significantly suppressed footpad swelling induced by local administration of cholera toxin, a potent phlogistic compound. The antibody response against the same immunogen was not influenced by denervation. Our results suggest that denervation of a mixed peripheral sensory/motor nerve abrogates the formation of both T cell-dependent and independent inflammatory responses.
Regulation of Eicosanoid Generation in Activated Macrophages
Authors: Lim W.H. , Stewart A.G.
Published: August 2009

Macrophage activation is accompanied by reductions in prostacyclin generation and platelet-activating factor (PAF) levels, but the mechanism has not been identified. We have investigated the involvement of glucocorticoid-sensitive mechanisms and endogenous PAF in this phenomenon. The synthetic glucocorticoid, dexamethasone (1 μM) reduced basal prostacyclin and PAF generation in resident, but not in activated macrophages. PAF receptor antagonists or dexamethasone reduced the basal, but not stimulation-induced prostacyclin generation in resident macrophages. Dexamethasone and PAF antagonists did not have synergistic inhibitory effects on prostacyclin generation by resident macrophages, and the reduction was less than that which accompanies macrophage activation. Thus, differences in the effects of PAF receptor antagonists and dexamethasone compared with macrophage activation on zymosan-induced prostacyclin synthesis indicate that factors other than PAF or glucocorticoid-sensitive mechanisms contribute to this phenomenon. Subsequent experiments with culture media conditioned by resident macrophages indicated the presence of a soluble factor which increases prostacyclin generation and appears to be absent in media conditioned by activated macrophages.
IgE-Positive Duodenal Mast Cells in Patients with Food-Related Diarrhea
Authors: Bengtsson U. , Rognum T.P. , Brandtzaeg P. , Kilander A. , Hansson G. , Ahlstedt S. , Hanson L.Å.
Published: August 2009

Thirty-seven consecutive adult patients with a history of adverse reactions to foods, manifested mainly as diarrhea, were investigated with skin prick test (SPT), IgE levels in serum, and the presence of IgE bound to mast cells in duodenal biopsy specimens. Nineteen percent had increased serum IgE levels indicating the presence of atopic disease and in 35% positive SPTs for one or several allergens related to their gastrointestinal symptoms were found. In 92% of the patients with positive SPTs to food, IgE-positive mast cells in duodenal biopsy specimens were found, twice as many as in patients with negative SPTs (47%). Forty-two percent of normal individuals without any adverse reactions to foods had IgE-bearing mast cells in their intestinal mucosa. The results showed that ‘arming’ of mast cells with IgE locally was relatively prominent but not consistent in the gut of patients with food-related diarrhea suggested to be allergic by positive SPT. Intestinal IgE-mediated hypersensitivity reactions could be of pathogenetic significance in most of these patients. However, since also half of the normal individuals were found to have IgE-positive intestinal mast cells, this phenomenon presumably also reflects a normal physiological defence mechanism.
The Effect of Systemic Treatment with Platelet-Activating Factor on the Migration of Eosinophils to Lung, Pleural and Peritoneal Cavities in the Guinea Pig
Authors: Colditz I.G. , Topper E.K.
Published: August 2009

Subcutaneous treatment of guinea pigs with platelet-activating factor (PAF) caused an increase in the prevalence of eosinophils in lavage fluid recovered from pulmonary airways, and pleural and peritoneal cavities. In PAF-treated animals, total numbers of eosinophils and macrophages in washings were positively correlated, thus there was no apparent competition between the two cell types for migration at traffic sites into body cavities. The results indicate that PAF acts centrally to enhance the migration of eosinophils and monocytes into body cavities, perhaps by inducing bone marrow release of both classes of leucocytes which may then migrate constitutively into lung, pleural and peritoneal cavities.
Cultures of Human Cord Blood Metachromatic Cells in Relation to Family History of Atopy, Development of Atopic Disease, Nasal Metachromatic Cells and Perinatal Factors
Authors: Borres M.P. , Ahlstedt S. , Björkstén B.
Published: August 2009

The appearance of basophilic cells by maturation from progenitors was studied in cultures of cord blood mononuclear cells (CB-MNC) from 83 newborns. In unstimulated cultures, the numbers of basophilic cells increased 5-fold after 14 days of cultivation. This increase and the cell numbers were similar in cultures from atopic individuals and controls. Other cultures were stimulated with conditioned medium (CM) prepared from 3-day cultures of blood cells from atopic individuals activated with allergen or with CM from the Mo leukemic cell line. The addition of such CM resulted in an increase in the number of basophilic cells, as compared to the cultures which were unstimulated (p <0.01). No correlation was found between the maturation of basophils and heredity for atopy, development of atopic disease, appearance of metachromatic cells in the nasal mucosa and perinatal factors, such as maternal infections, perinatal stress, birth weight, month of birth and IgE levels. The study confirmed that basophilic cells can be driven to mature in cultures of CB-MNC, although the maturation did not seem to depend on atopic predisposition as indicated by family history of allergy and CB IgE levels nor on symptoms and signs of atopic disease during the first 18 months of life. Therefore, the predictive value of elevated basophilic cell numbers in CB or CB-MNC cultures with regard to allergic disease seemed to be limited.
Fibroblast Proliferation Factors in Pulmonary Granuloma Induced by Trichosporon cutaneum in Rabbits: Presence of a Lymphocyte-Derived Fibroblast Proliferation Factor and Its Functional Specificity
Authors: Saita Naoki , Ando Masayuki , Araki Shukuro , Yoshinaga Masaru
Published: August 2009

The fibroblast proliferation activity (FPA) in pulmonary granulomatous lesions in rabbits which were exposed once (primary response) or twice (secondary response) to Trichosporon cutaneum was examined using R9ab, a rabbit fibroblast cell line cell, and fibroblasts from the lesions of the primary and secondary responses. The FPA in lung extracts and cell-free culture supernatants of bronchoalveolar lavage cells from the secondary response was more evident than that from the primary response. FPA from the primary response were recovered at about 60, 18, and 4.5 kD and those from secondary response at about 60, 26, 18, and 4.5 kD on Sephadex G-75 gel filtration. Among the FPA, the activity with a molecular weight of 26 kD and a pI of 7.0 was derived from lymphocytes, whereas the other activities were derived from macrophages. The macrophage-derived fibroblast proliferation factors (FPF) enhanced proliferation of fibroblasts from the lesions of both primary and secondary responses, while the lymphocyte-derived FPF enhanced only proliferation from the secondary response. It was further found that lymphocyte-derived FPF could chemotactically attract fibroblasts from the secondary but not the primary response, indicating functional specificity of lymphocyte-derived FPF on fibroblasts in the secondary response. The present results suggest that this lymphokine with fibroblast proliferation and chemotactic activity plays an important role in the granuloma formation in the secondary response to T. cutaneum.
IgE-Mediated Inhalant Allergy against Human Corticotropin-Releasing Hormone
Authors: Kleine-Tebbe J.K. , Wahl R. , Dierks K. , Kunkel G.
Published: August 2009

A 25-year-old female developed IgE-mediated sensitization against human recombinant corticotropin-releasing hormone (CRH) with symptoms of allergic rhinoconjunctivitis and bronchial asthma. The occupational allergy was proved by positive skin prick test, bronchial provocation, dose-dependent histamine release, RAST measurements with CRH allergen (RAST class 3) and RAST inhibition. Using the immunoblot technique, a single allergen band with a molecular weight of <14.4 kD in the range between the isoelectric point 5.2 and 5.7 was detected for the CRH extract. Since no endocrinological and behavioral disorders were found, increased CRH-specific IgE was not able to influence the regulatory control of this neuropeptide. After 18 months of avoiding the occupational CRH exposure allergen-specific histamine release and RAST were negative.
Immunoglobulin E in the Feces of Children and Adolescents from Some Tropical and Subtropical Countries
Authors: Kolmannskog Svein , Jansson Staffan , Häggblom Lars , Mentzing Lars-Olof , Hvidsten Dag , Haneberg Bjørn
Published: August 2009

Eighteen of 27 individuals, aged from 6 months to 19 years (mean 5 years, 7 months), from countries in the tropics or the subtropics had either intestinal parasitic infestations or intestinal enteropathogenic bacterial infections or both. Fourteen of those with intestinal pathogens had detectable concentrations of IgE in their fecal extracts, ranging from <0.5 to 420 IU/ml extract (mean 33 IU/ml). This rate of occurrence was significantly higher than the number of IgE-positive fecal extracts in a group of 54 healthy nonallergic Norwegian children (p <0.001), but did not differ from that of a group of 40 allergic children (p >0.20). The individuals with intestinal helminthic infection had the highest fecal IgE concentrations. Of the 9 individuals who did not have any demonstrable intestinal pathogen, low concentrations of IgE could be detected in feces from only 2, which did not differ from the rate in the healthy Norwegian controls. The concentrations of IgE in the feces of the subjects from tropical/subtropical regions correlated linearly with the corresponding serum concentrations of IgE (r = 0.69; p <0.001). The results indicate that the combined load of intestinal pathogens, including helminths, protozoa, and enteropathogenic bacteria, may stimulate IgE production in the gut.
Pharmacology of Nasal Provocation with Bradykinin: Studies of Tachyphylaxis, Cyclooxygenase Inhibition, α-Adrenergic Stimulation, and Receptor Subtype
Authors: Churchill Laurie , Pongracic Jacqueline A. , Reynolds Curt J. , Naclerio Robert M. , Proud David
Published: August 2009

We have evaluated mechanisms by which nasal provocation with bradykinin may induce symptoms of rhinitis. Repeated nasal challenges with 100 μg of bradykinin led to reproducible increases in symptoms and in vascular permeability. Premedication with aspirin did not alter bradykinin-induced responses. Topical application of the α-adrenergic agonist oxymetazoline significantly reduced bradykinin-induced subjective nasal congestion scores, but did not lead to a significant decrease in total symptoms or in vascular permeability. Finally, the B1 kinin receptor agonist des-Arg9-bradykinin (1 mg) was totally ineffective in inducing symptoms or increasing vascular permeability. Thus, nasal provocation with bradykinin leads to induction of symptoms and increased vascular permeability, presumably via stimulation of B2 kinin receptors, and is not dependent on prostanoid generation.