bluuebunny/crossref_metadata_2025 huggingface dataset:
Activity of a Novel Hydroquinone Inhibitor of Leukotriene Synthesis (U-66,858) in the Rhesus Monkey Ascaris Reactor
Authors: Johnson Herbert G. , Stout Barbara K.
Published: August 2009

The IgE-mediated hypersensitivity to Ascaris antigen in reactor rhesus primates was used to assess the pharmacologic profile of U-66,858 (1-acetoxy-2-n-butyl-4-methoxy-naphthalene). When the compound was given by the oral route, it showed dose-related inhibition of resistance (RL) and compliance (Cdyn) changes. When the compound was given by the aerosol route, it showed dose independent inhibition. In 15 animals, aerosols (52 ± 32 to 53 ± 10% for RL, p = 0.05 and 45 ± 19 to 28 ± 19% Cdyn inhibitions, p = 0.05) for 5.0–0.1% aerosol. By the oral route, inhibition was seen at 1–4 h following administration. In 5 animals, oral doses of 10 and 5 mg/kg inhibited (RL by 98 ± 2 to 78 ± 1.5 %, p = 0.01 and Cdyn by 75 ± 17 to 60.9 ± 9.1 %, p = 0.05) by 10 and 5 mg/kg U-66,858, respectively. The in vivo demonstration of inhibition of pulmonary bronchoconstriction by this compound, in a model known to be leukotriene sensitive, coupled with its potent in vitro inhibition of 5-lipoxygenase enzymes, suggests this compound may be of use in 5-lypoxygenase-mediated models of asthma.
Inhibition of Vascular Permeability Increase in Mice
Authors: Inagaki Naoki , Miura Toru , Nagai Hiroichi , Ono Yutaka , Koda Akihide
Published: August 2009

Effects of glucocorticoids on IgE antibody-mediated 48-hour homologous passive cutaneous anaphylaxis (PCA) and skin reactions caused by mediator releasers and vascular permeability increasing factors were investigated comparatively. Both PCA and skin reactions were evoked in the mouse ear and these reactions were quantitatively evaluated by measuring the amount of dye extravasated into the ear. The glucocorticoids hydrocortisone, prednisolone and dexamethasone inhibited the PCA significantly. The maximum inhibitory effects of these glucocorticoids were obtained when administered 8 h prior to the antigenic challenge. Dexamethasone significantly inhibited the skin reactions caused by compound 48/80, Ca ionophore A 23187 and hypotonic salt solution. Dexamethasone also significantly inhibited the skin reactions caused by histamine, serotonin, platelet-activating factor, leukotriens C4 and D4, and bradykinin. The maximum inhibitory effects of dexamethasone on these skin reactions were observed when administered 12–6 h before. These results support the previous observations that glucocorticoids inhibit the increase of vascular permeability caused by various stimuli, and indicate that the inhibition of vascular permeability increase contributes at least in part to the inhibitory effects on the PCA and the mediator releaser-induced skin reactions. Furthermore, the inhibition of vascular permeability increase by glucocorticoids might play an important role in their anti-allergic actions.
Induction of T-Helper Cell Activity by Fragments of Rye Grass Pollen Extract Produced by Digestion with Chymotrypsin
Authors: Standring R. , Lavender E.A. , Wheeler A.W. , Spackman V.M. , Moran D.M.
Published: August 2009

Rye grass pollen extract was digested by chymotrypsin to produce fragments with a molecular weight below 10,000, as demonstrated by polyacrylamide gel electrophoresis. Chymotryptic fragments did not react with either human or mouse IgG antibodies specific for rye grass pollen, nor did they induce an antibody response in mice with specificity for the parent extract. However, macrophage-presented fragments retained the ability to react with rye-specific T cells in a lymphoproliferation assay. Furthermore, these fragments induced the development of splenocytes capable of supporting dinitrophenyl specific antibody production. This implies that the fragments still react with, and induce, rye grass pollen extract-specific T-helper cells. The possibility that such fragments might have potential for use in immunotherapy for the specific treatment of allergy is discussed.
Human Monoclonal Antibody against Human Lymphocytic Cells
Authors: Harpprecht J.H. , Hansmann M.L. , Westphal E. , Müller-Ruchholtz W.
Published: August 2009

Human monoclonal antibodies may replace human or xenogeneic antisera and mouse monoclonal antibodies for therapeutic applications. The human IgM monoclonal antibody Ha6D3 was produced after in vitro immunization and fusion with a mouse myeloma. Its reactivity against human normal and leukemic cells was investigated in cytotoxicity assays, and the antigen distribution in normal tissues was investigated with biotinylated Ha6D3 and avidin-peroxidase complexes. It was shown that Ha6D3 reacts preferentially with human lymphocytic cells. Only moderate reactions with epithelial cells in some organs were observed in cryostat sections, but because of poor accessibility in vivo these reactions were considered to be negligible.
Comparison of Guinea Pig IgE Antibodies Estimated by ELISA with Those Estimated by Passive Cutaneous Anaphylaxis
Authors: Ito Koji , Ishii Akira , Yamashita Naomi , Miyamoto Terumasa , Watanabe Naohiro
Published: August 2009

Guinea pig IgE antibodies to ovalbumin or mite were measured by enzyme-linked immunosorbent assay (ELISA), and the levels of IgE antibodies to mite were compared with titers of passive cutaneous anaphylaxis (PCA). The results of ELISA were highly reproducible when the assays were done in the same microtiter plate and on the same day. The levels of IgE antibodies to mite determined by ELISA correlated well with the PCA titers (n = 29, r = 0.70, p <0.001). The measurement of IgE antibodies by ELISA saved much time in comparison with PCA which needs at least 7 days for getting results.
Effect of Antihistamines on Antigen-Induced Increase of Rat Tracheal Mucous Gel Layer Thickness
Authors: Yanni J.M. , Foxwell M.H. , Whitman L.L.
Published: August 2009

The effect of orally administered H1 and H2 antihistamines on antigen-induced changes in tracheal mucous gel layer thickness of actively sensitized rats was determined. Cimetidine and ranitidine, H2 antagonists, produced dose-dependent inhibition of antigen-induced increase in gel thickness at doses ranging from 0.32 to 3.16 and from 0.10 to 1.0 mg/kg, respectively. H2- antagonists – like chlorpheniramine, diphenhydramine, and pyrilamine which possess anticholinergic properties – tended to enhance the antigen-induced gel thickening in a dose-dependent fashion, while astemizole and terfenadine had no effect. These data indicate that an antigen-induced increase of rat tracheal mucous gel layer thickness may result from stimulation of the H2 receptor, while histamine operating at the H1 receptor does not play a role. Therefore, an antihistamine that possesses both H1 and H2 antagonist properties while lacking anticholinergic properties appears to be the most appropriate for use in patients with asthma and associated bronchorrhea.
Increased Hyaluronan (Hyaluronic Acid) Levels in Bronchoalveolar Lavage Fluid after Histamine Inhalation
Authors: Söderberg M. , Bjermer L. , Hällgren R. , Lundgren R.
Published: August 2009

Hyaluronan (hyaluronic acid) appears in low concentrations in bronchoalveolar lavage fluid from healthy individuals, while increased amounts have been reported in lavage fluid from patients with interstitial lung diseases and allergic asthma. We have earlier reported a strong correlation between the appearance of lavage fluid mast cells and hyaluronan in patients with sarcoidosis and extrinsic allergic alveolitis. The central role of the mast cell in allergic asthma is well documented. In this study we have investigated if challenge with inhaled histamine, a major mast cell component, could influence the appearance of hyaluronan in bronchoalveolar lavage fluid. A more than twofold increase of hyaluronan was seen 24 h after challenge with histamine. This increase correlated with a less pronounced increase of albumin in lavage fluid. Histamine challenge also induced an increase of mast cells, lymphocytes, and granulocytes in the lavage fluid. The observed histamine effect on the hyaluronan recovery during lavage might be explained by a histamine-mediated leakage of interstitial fluid, rich in hyaluronan, to the alveolar space. Mast cell degranulation of histamine may partly underlie the appearance of increased amounts of hyaluronan in lavage fluid from patients with interstitial lung diseases and allergic asthma.
Inhibition of cAMP Increase by an Anti-Allergic Agent, NCO-650, during Histamine Release
Authors: Takei M. , Matumoto T. , Endo K. , Muramatu M.
Published: August 2009

Antigen and concanavalin A (Con A) induced an increase in cAMP and histamine release from rat peritoneal mast cells. In a dose-dependent manner, the compound, NCO-650, significantly inhibited both the initial and secondary increases in cAMP stimulated by antigen, anti-IgE and Con A in rat peritoneal mast cells. IC50 values of NCO-650 for cAMP increase stimulated by antigen, anti-IgE and Con A were 3.8, 3.4 and 2.8 μM, respectively.
Occurrence of Histamine-Production-Increasing Factor in the Postanaphylactic Phase of Allergic Inflammation
Authors: Hirasawa Noriyasu , Ohuchi Kazuo , Kawarasaki Kimiko , Watanabe Masako , Tsurufuji Susumu
Published: August 2009

Experimental study on histamine liberation in a postanaphylactic phase of allergy was carried out employing an air pouch model of allergic inflammation in rats. The antigen used was azobenzenearsonate-conjugated acetyl bovine serum albumin. Synthesis and liberation of histamine took place in the inflammatory pouch in the dorsum of the allergic rats, and brought about a gradual rise in the histamine level in the pouch fluid with a peak at 24 h after the antigen challenge. The time course of the histamine level in the pouch fluid was quite similar to that of histidine decarboxylase activities in the inflammatory tissues. α-Fluoromethylhistidine reduced the histamine level in the postanaphylactic phase, although it had been ineffective in the anaphylactic phase. A substance capable of increasing histamine production by bone marrow cells was found in the pouch fluid of allergic rats, while it was absent in the normal rat serum and pouch fluid of nonsensitized rats. The histamine-production-increasing activity rose until 24 h after the antigen challenge, but fell at 48 h in parallel with changes both of histamine levels in the pouch fluid and histidine decarboxylase activity in inflammatory tissues. The histamine-production-increasing factor is thought to be a protein, since it was inactivated by treatment with heat (70 °C for 30 min) or trypsin. Its molecular weight was estimated to be between 25,000 and 40,000.
Human Seminal Plasma Suppresses Delayed-Type Hypersensitivity Responses to Intravaginally Deposited Sheep Red Blood Cells and Sperm: Separation of Immunosuppressive Factors
Authors: Lee Hern-Ku , Ha Tai-You
Published: August 2009

Although significant progress has been made in identifying the immunosuppressive factors in seminal plasma (SP) and their possible action in vitro, the potential role of SP in naturally occurring normal immune responses in vivo is less certain. Human SP or its fractions, administered 5 or 10 times at 3-day intervals into the mouse vagina simultaneously with washed human sperm or sheep red blood cells, suppressed the delayed-type hypersensitivity reactions to footpad injection of the antigens. However, SP failed to suppress antibody formation to these antigens in the applied experimental conditions. In an in vitro study, SP suppressed the proliferation of human peripheral blood mononuclear cells to phytohemagglutinin. This suppression of in vitro proliferation by SP was mediated by materials of both low (LMW) and high molecular weight (HMW). Among the HMW materials, a factor with approximately 1,500 kilodaltons, partially purified by DEAE-cellulose chromatography and gel filtration, exhibited the most potent suppressor activity in vitro and in vivo. The suppressive activities of SP or its fractions were not abolished by treatment with both heat (95 °C for 10 min) and trypsin (1.0 mg/ml, 37 °C for 4 h). These findings indicate that SP could contribute to the development of suppressed cellular immunity to sperm; immunosuppressive actions of SP are mediated by at least two distinct factors in vivo as well as in vitro.
Serum Neopterin in Patients with X-Linked and Acquired ‘Common Variable’ Hypogammaglobulinaemia
Authors: Harland C. , Shah T. , Webster A.D.B. , Peters T.J.
Published: August 2009

Serum neopterin was measured in patients with acquired ‘common variable’ hypogammaglobulinaemia (CVH), X-linked agammaglobulinaemia (XLA) and healthy subjects. There was a highly significant increase in neopterin levels in the CVH patients as compared with that of the other groups, particularly in those CVH patients with non-A non-B or granulomatous hepatitis. There was no association between raised neopterin levels and chronic infective lung disease. Since chronic viral infections are associated with raised serum neopterin, this data add some support to a viral aetiology for CVH.
Effect of Systemic and Orally Administered Iota-Carrageenan on Ovalbumin-Specific Antibody Response in the Rat
Authors: Coste M. , Dubuquoy C. , Tomé D.
Published: August 2009

Iota-carrageenans are high molecular weight polygalactans commonly used in the food industry. Their immunomodulating effects were examined on the reaginic and IgG ovalbumin-specific responses after systemic or oral administration to Brown Norway rats. Intraperitoneal injection of ovalbumin with either iota-carrageenan or alum induced both a reaginic and IgG response. Reaginic antibodies were detected in the primary response with alum, but only in the secondary response with iota-carrageenan. Oral tolerance to ovalbumin was similarly induced whether the protein was given alone or admixed in solution with iota-carrageenan. These results confirmed the systemic adjuvant action of iota-carrageenan described earlier, and showed that this effect did not take place when orally administered.
A Multifunctional Cytokine (IL-6/BSF-2) and Its Receptor
Authors: Hirano Toshio , Taga Tetsuya , Yamasaki Katsuhiko , Matsuda Tadashi , Tang Bo , Muraguchi Atsushi , Horii Yasuhiro , Suematsu Sachiko , Hirata Yuuichi , Yawata Hideo , Shimizu Masatoshi , Kawano Michiaki , Kishimoto Tadamitsu
Published: August 2009

Interleukin 6 (IL-6)/B cell stimulatory factor 2 is a multifunctional cytokine produced by both lymphoid and nonlymphoid cells. IL-6 regulates immune response, acute phase reaction, and hematopoiesis. It was found that IL-6 production by T cells is dependent on macrophages, and IL-6 is one of essential factors for pokeweed mitogen induced immunoglobulin production. Both high- and low-affinity IL-6 receptors were identified. The molecular cloning of IL-6 receptors demonstrated that this receptor is a member of the immunoglobulin superfamily. The deregulated production of IL-6 is suggested to be involved in the pathogenesis of autoimmune diseases and in the development of multiple myeloma.
Eosinophils and Human Disease
Authors: Gleich G.J. , Ottesen E.A. , Leiferman K.M. , Ackerman S.J.
Published: August 2009

The likely roles of the eosinophil leukocyte in human disease are reviewed. The eosinophil is richly endowed with toxic cationic proteins and is able to mount a respiratory burst. Thus, eosinophils have the capability to damage various targets, and evidence exists that they do so during helminth infections and during the course of many hypersensitivity diseases. Here we discuss the role of the eosinophil in human onchocerciasis with particular attention to the Mazzotti reaction. We also discuss other diseases where eosinophil degranulation is seen, especially cutaneous diseases. Finally, the possible role(s) of the granule major basic protein in human pregnancy is noted.
Interactions between Neurotransmitters and Inflammatory Cells in the Airways
Authors: Pauwels Romain , Joos Guy , Kips Johan , Van Der Straeten Marcel
Published: August 2009

Neuropeptides and purines are possible autonomic neurotransmitters. Both tachykinins (neurokinin A, substance P) and adenosine cause acute airway narrowing by synergistic activation of airway mast cells and postganglionic vagal nerve endings.
Interleukin 4 Acts on Both High- and Low-Density Murine B Cell Subpopulations to Induce IgE and IgG1 Synthesis in vitro
Authors: Lebrun Philippe , Lucas Alexander H. , McKenzie Douglas T. , Spiegelberg Hans L.
Published: August 2009

Murine B cells were activated for 24 h with either lipopolysaccharide (LPS) or polyribosyl-ribitolphosphate (PRP), followed by addition of interleukin 4 (IL-4) and the immunoglobulin isotypes secreted into the supernatant quantitated. Without IL-4, both LPS and PRP induced mainly IgM and IgG3 and no IgE secretion. Addition of IL-4 to both LPS- and PRP-activated cells decreased the IgM and IgG3 secretion and induced a large IgG1 production. In contrast to IgG1, only LPS-activated cells secreted large amounts of IgE, demonstrating that the nature of the polyclonal B cell activator also plays an important role in the IL-4 induced IgE formation. The effect of LPS and IL-4 on high- and low-density sIgM+/sIgD+ cells was also investigated. LPS and IL-4 induced IgGl and IgE secretion by both populations. Low-density B cells from mice infected with the parasite Nippostrongylus brasiliensis formed more IgE than low-density B cells from normal mice, presumably because these mice have more in vivo preactivated B cells committed to IgE formation. The data show that IL-4 can act on both small high-density resting B cells as well as on in vivo preactivated low-density B cells to induce IgGl and IgE secretion.
Formation of IgE-Binding Factors by Lymphocytes of HIV-Infected Patients
Authors: Carini C. , Margolick J. , Yodoi J. , Ishizaka K.
Published: August 2009

Peripheral blood mononuclear cells of human immunodeficiency virus infected patients were cultured in the presence or absence of 10 μg/ml human IgE, and culture filtrates were fractionated on IgE-Sepha-rose. IgE-binding factors were assessed in the acid eluate fraction from IgE-Sepharose by both rosette inhibition assay and radioimmunoassay. Among 22 cases studied, mononuclear cells from 9 patients formed IgE-binding factors in the absence of IgE, and those of 13 cases formed the factors upon incubation with IgE. The major cell source of IgE-binding factors was T cells. In 2 cases of human immunodeficiency virus infection, Fcε receptors were detected on both Leu-2+ and Leu-3+ T cells.
Conditioned Media from Cultured Blood Cells of Atopic Individuals Can Induce Differentiation in the Human Basophilic Leukemia Cell Line KU812
Authors: Matsson P. , Almlöf I. , Nilson K. , Ahlstedt S.
Published: August 2009

The basophilic propagating activity was determined in conditioned media obtained from cell cultures of mononuclear cells from atopic and healthy individuals. The activity was analyzed as the capacity to induce differentiation in the human basophilic cell line KU812. The KU812 cells responded primarily to cultured media with histamine production and secondarily with granulation. Eight atopic individuals, 3 of whom having mild symptoms, with known birch allergies were selected together with 3 control individuals. Total and specific IgE were analyzed in sera, and basophil and eosinophil counts were determined from blood smears after Wright’s staining. Significant differences between the symptomatic atopic individuals and the control group were obtained for eosinophil counts (p < 0.05) and in the KU812 basophilic differentiation activity assay (p < 0.01). No single test could significantly discriminate between symptomatic and nonsymptomatic individuals, but the KU812 cell assay in combination with the eosinophil count clearly distinguished the symptomatic individuals from the control group. Increased levels of IgE specific to birch allergen were only obtained in the atopic individuals (p < 0.001). No difference in basophilic propagating activity was observed with supernatants from cells incubated with birch pollen allergen. Serum tested for basophilic propagating activity showed no or decreased values of inducing histamine production in the KU812 cell line. In conclusion, the KU812 assay for basophilic propagating activity was the most useful discriminating test to select symptomatic atopic individuals from nonsymptomatic atopic and control individuals.
Free Radicals Induce Ischemia-Reperfusion Injury and Histamine Release in the Isolated Guinea Pig Heart
Authors: Masini Emanuela , Giannella Eliana , Palmerani Beatrice , Pistelli Alessandra , Gambassi Francesco , Mannaioni Pier Francesco
Published: August 2009

Free radicals are produced by perfusion of isolated guinea pig heart with FeCl3/ADP (10 μM/100 μM) and/or occlusion and opening of the left anterior descending coronary artery. Cardiac histopathology was correlated with histamine and lactate dehydrogenase release and with malondialdehyde production. A differential release of histamine and lactate dehydrogenase in the perfusate was detected, showing a preferential liberation of histamine in the reperfusion phase. The increase in lipid peroxidation product in left ventricular tissues after left coronary artery occlusion was maximal at the end of ischemia.
Ultraviolet A Inhibits Histamine Release from Human Peripheral Leukocytes
Authors: Ring Johannes , Przybilla Bernhard , Eberlein Bernadette
Published: August 2009

Irradiation of human peripheral leukocytes with ultraviolet A (UVA) induced a significant and dose-dependent reduction of anti-IgE or Ca-ionophore-stimulated histamine release without consistent influence upon C5a-induced release reactions. This effect was equally demonstrable in atopies and controls. In the presence of the radical scavenger superoxide dismutase, the UVA-induced inhibition of anti-IgE-induced histamine release was abolished. Under the conditions used, UVB exposure did not result in relevant changes of in vitro histamine release.
Chronic Glomerulonephritis: Inflammatory Mediators Stimulate the Collagen Synthesis in Glomerular Epithelial Cells
Authors: Hänsch G.M. , Torbohm I. , Rother K.
Published: August 2009

C5b-9 membrane attack complexes of complement (MAC) stimulate the production of type IV collagen in cultures of human glomerular epithelial cells. Together with other known effects of MAC interaction with glomerular cells, the complex is ascribed a role in the progress of acute glomerulitis into the chronic nephritic state.
Conjunctival Provocation Test as a Model for the Study of Allergy and Inflammation in Humans
Authors: Bonini Sergio , Bonini Stefano , Berruto Annagrazia , Tomassini Margherita , Carlesimo Sara , Bucci Massimo G. , Balsano Francesco
Published: August 2009

The clinical response after allergen challenge and immunologic mechanisms leading to tissue inflammation have been extensively studied in the skin, nose and lung of allergic subjects. The present paper reviews personal studies aimed at evaluating clinical, cellular and humoral events after administration of specific allergen to the eye. Specific conjunctival provocation tests performed in grass-sensitive patients caused persisting inflammatory changes in conjunctival scrapings and tear fluid with a significant accumulation of different inflammatory cells depending on the time of observation (neutrophils, 20 min; eosinophils, 6 h; neutrophils, eosinophils and lymphocytes, 12–24 h after provocation). Increasing the dose of allergen resulted in a dose-dependent increase in the number of inflammatory cells recruited. When high doses of allergen were used, the challenge not only induced late-phase histological changes, but also clinical symptoms 6–10 h after provocation. Several mediators of allergic inflammation, such as histamine, C3a des-Arg, leukotrienes B4 and C4, were also present and could be measured in tears after allergen challenge. Our studies represent the first evidence in humans that a late phase of allergic reaction occurs in the eye. They also suggest that the conjunctival provocation test may represent a model for the study of cells and mediators involved in the pathophysiology of allergic inflammation as well as of its pharmacologic modulation.
Effect of Long-Term Administration of Platelet-Activating Factor on Pulmonary Responsiveness and Morphology in the Guinea Pig
Authors: Mencia-Huerta Jean-Michel , Touvay Caroline , Pfister André , Braquet Pierre
Published: August 2009

To further substantiate the possible role of platelet-activating factor (PAF) in the development of bronchial hyperreactivity, Alzet osmotic minipumps loaded with the autacoid or solvent alone were placed under the back skin of male Hartley guinea pigs and connected to the jugular vein for 15 days. As compared to the animals treated with solvent alone, guinea pigs receiving PAF (20 μg/kg/h, 15 days) exhibited a hyperresponsiveness to histamine that was not observed in those simultaneously treated with PAF and the PAF antagonist BN 52021. Lungs from PAF-treated animals were congestive in appearance, bronchi and bronchioli were contracted, Reisseisen muscles were markedly hypertrophied, and a muciparous metaplasia of the endothelium was observed. The number of eosinophils was significantly increased in the parenchyma, as was the number of mast cells in the peribronchial zones in the lungs from guinea pigs chronically treated with PAF. Lungs from control animals did not show morphologic alterations or eosinophil and mast cell infiltration. These data indicate that long-term treatment with PAF induces profound alterations in the respiratory system, resembling those observed in asthmatic patients. This result is in keeping with the possible role of this autacoid in the development of bronchial hyperreactivity.
Molecular Genetics of Human Immune Responsiveness to Lolium perenne (Rye) Allergen, Lol p III (Short Communication)
Authors: Ansari Aftab A. , Freidhoff Linda R. , Marsh David G.
Published: August 2009

Lol p II and III are each about 11-kD protein allergens from the pollen of Lolium perenne (rye grass). We have found that human immune responses (IgE and IgG antibodies) to both proteins are significantly associated with HLA-DR3. In addition, the two proteins are cross-reactive with the antibodies in many human sera (about 84% human sera showed the cross-reactivity). We have determined > 90% of the amino acid sequences of the two proteins and found that they are at least 54% homologous. Berzofsky found that 75% of the 23 known T cell sites in various proteins had an amphipathic structure. Our analysis by the same method showed that both Lol p II and III have a major region of amphipathicity (at residues 61–67, Lol p III numbering) which might contain sites for binding to an la molecule and a T cell receptor. This region is identical between Lol p II and III, except for an Arg-Lys substitution, and could account, in part, for the DR3 association with responsiveness to both molecules. An interesting difference between the two proteins is that immune response to Lol p III is associated with DR5 (in addition to DR3), whereas no DR5 association is found in the case of Lol p II. One possibility is that Lol p III has an additional site which binds to the DR5 la molecule. Lol p III indeed has a second highly amphiphathic peptide, 24–30 (Lol p III 24 R P G D T L A 30), which is different and not amphipathic in Lol p II. Therefore, the results of these analyses are consistent with our observations that DR3 is associated with immune responses to both Lol p II and III, but DR5 is associated with immune response to only one of them, Lol p III. Further experiments are required to examine these postulates.
Specificities of IgE and IgG Antibodies in Patients with Birch Pollen Allergy
Authors: Jarolim Erika , Rumpold Helmuth , Endler Thomas , Schlerka Gabriele , Ebner Herwig , Scheiner Otto , Kraft Dietrich
Published: August 2009

58 sera from patients with established birch pollen allergy showed characteristic antibody-binding patterns in immunoblotting experiments. Regarding IgE, 56/58 patients recognized a protein of molecular weight (MW) 17 kilodaltons (kD), previously defined as Bet v I. 23/58 patients in addition reacted with a variety of 11 minor allergens with MWs ranging from 13 to 68 kD. A 13-kD protein was proved to represent an independent minor allergen. IgG binding in patients and healthy individuals was more pronounced on the minor allergens than on Bet v I. 3 different allergens were not detected by IgG of healthy individuals. In two-dimensional electrophoresis/immunoblot, a monoclonal antibody and human IgE (in both cases directed against Bet v I) detected a very similar cluster of spots, probably representing isoallergens of Bet v I.
Inhalant Allergy in Asthmatic Children: Skin Prick Test, Radioallergosorbent Test and Chemiluminescent Assay Compared with Allergen Levels in Their Mattress Dusts
Authors: Price Jill A. , Reiser J. , Longbottom Joan L. , Warner J.O.
Published: August 2009

Mattress dusts from the beds of 51 asthmatic children with positive skin tests to house dust mite were assayed for Der p I, Fel d I and certain viable fungi. The results of skin tests to grass, cat, dog, Alternaria, Aspergillus, Cladosporium and Penicillium, radioallergosorbent tests to cat, mite, dog and grass and the chemiluminescent assay were compared and correlations made with allergen concentrations in the dust. The sensitivity of the three tests appeared comparable (percentage agreement = 54.5–94), however, an increased level of allergen in the mattress dust was not a good indicator of the degree of sensitization of the child (p > 0.05).
Characterization of Immunologically Important Antigens and Allergens of Aspergillus fumigatus
Authors: Longbottom J.L. , Harvey C. , Taylor M.L. , Austwick P.K.C. , Fitzharris P. , Walker C.A.
Published: August 2009

Using a variety of immunochemical methods, including quantitative immuno-electrophoretic techniques, combined with gel filtration and iso-electric focusing, and production of monospecific antisera for identification and affinity purification, 4 major components of Aspergillus fumigatus have now been partially characterized. Numbering of these was derived from a reference allergic bronchopulmonary aspergillosis (ABPA) self-crossed radio-immuno-electrophoresis pattern of reactivity. Two major intracellular/cytoplasmic, concanavalin A (Con A)-binding antigens, Ag 7 and Ag 13, of molecular weights 150–200 and 70 kilodaltons (kD), respectively, were confirmed to be of importance for both ABPA and aspergilloma in specific sandwich enzyme-linked immunosorbent assays. A rapidly released component, Ag 5, of molecular weight 35 kD, proved both antigenic and allergenic, with aspergilloma patients having especially high-titre IgG antibodies. The major allergenic component Ag 3, of molecular weight 24 kD by gel filtration and 18 kD by SDS-PAGE was, like Ag 5, relatively heat-labile and non-Con-A-binding. Interestingly, T cell clones have been identified which respond primarily to an 18-kD fraction.
Flow-Cytometric Analysis of Increased IgE Uptake by Normal Eosinophils following Activation with PAF-Acether and Other Inflammatory Mediators
Authors: Walsh G.M. , Nagakura T. , Iikura Y.
Published: August 2009

Using flow-cytrometric analysis and a fluorescein-conjugated anti-IgE antibody, we have investigated whether normal-density human eosinophils will bind greater amounts of native IgE following activation with platelet-activating factor (PAF), leukotriene B4 (LTB4) and histamine. Incubation with PAF resulted in a large dose- and time-dependent increase in IgE binding, optimal at 10––7M and 30 min, respectively. LTB4 and histamine gave lower but significant increases in IgE binding. Enhanced binding of IgE by activated normal-density eosinophils is probably a consequence of enhanced FcεRII receptor expression, suggesting a functional role for this receptor in allergic inflammation.
Potential Role of Anti-IgE Antibodies in vivo
Authors: Stadler Beda M. , Nakajima Kazunori , Yang Xiadong , de Weck Alain L.
Published: August 2009

Murine monoclonal antibodies which recognize similar epitopes as the naturally occurring human IgG anti-IgE antibodies were used to study their role in interfering with the effector functions of IgE. Two types of antibodies were found which were either anaphylactogenic or did not release histamine from human basophils. However, both types of antibodies were capable of inhibiting binding of IgE to FcεRII. Furthermore, the nonanaphylactic antibody was capable of removing IgE from FcεRII+ cells, but no antibodies were found which removed IgE from FcεRI+ cells. Thus, anti-IgE antibodies may interfere with the pathophysiological role of IgE.
Inhibition of Human Eosinophil Chemotaxis and of the IgE-Dependent Stimulation of Human Blood Platelets by Cetirizine
Authors: De Vos Christine , Joseph Michel , Leprevost Corinne , Vorng Han , Tomassini Margherita , Capron Monique , Capron André
Published: August 2009

Cetirizine is a new anti-allergic compound with a potent, long-acting, and specific antihistaminic property. Strongly active in the therapy of urticaria and seasonal or perennial rhinitis, it has been shown to inhibit the in vivo eosinophil attraction at skin sites challenged with allergen in atopic patients. In the present work, we confirmed that, at a therapeutical concentration, this molecule had a potent inhibitory action in vitro on eosinophil chemotaxis induced either by N-formyl-Met-Leu-Phe or platelet-activating factor and also on the IgE-dependent stimulation of platelets. These observations appear in favour of a possible role for cetirizine in the modulation of inflammatory cell interactions in allergic processes.
Relationship between Bacteria and IgE
Authors: Levy David A. , Dorat Anne , Pinel Anne-Marie , Normier Gerard , D’Hinterland Lucien Dussourd , David Bernard
Published: August 2009

In this preliminary report, we describe our inability to induce IgE antibody to a well-characterized bacterial component, the membrane proteoglycan of Klebsiella pneumoniae and its major protein fraction FIII-B in BALB/c mice. In contrast, an immunomodulatory effect of membrane proteoglycan of K. pneumoniae on the IgE and IgG antibody responses to ovalbumin could be demonstrated.
IgG and IgE Antibodies after Immunotherapy with Bee and Wasp Venom
Authors: Kemeny D.M. , Lessof M.H. , Patel S. , Youlten L.J.F. , Williams A. , Lambourn E.
Published: August 2009

IgG and IgE antibody levels have been followed for a period of 2 years in patients receiving immunotherapy with bee and wasp venom. 106 adult patients who had had anaphylactic reactions to wasp stings had initially low IgG antibody levels to wasp venom which rose with therapy (p < 0.001). IgE antibody levels also showed an initial rise but subsequently fell (p < 0.001). The pattern was similar to that previously reported in children who had had anaphylactic reactions to bee stings, but who, after a course of immunotherapy, were able to tolerate stings with impunity. 60 adults who had had anaphylactic reactions to bee stings showed a different pattern, with initially high IgG antibody levels which did not rise further. Since two thirds of this group were beekeepers or members of beekeepers’ families, the high initial IgG antibody levels could have been a response to the frequent stings to which such individuals are prone. The fact that high levels did not protect against anaphylaxis shows, however, that the classical concept of ‘blocking antibody’ is in need of revision.
Immune Reactions in a Changing Environment
Authors: Goldstein Robert A.
Published: August 2009

Environmental hazards occurring as an undesirable consequence of economic progress, urbanization and pollution have become a worldwide concern. In the US, this is evident from the campaign against smoking which has focused attention on the lung in part because the lung as a target organ is constantly exposed to many visible environmental hazards. On the other hand, environmental hazards which are not lethal, but cause their effects in an insidious fashion, may be difficult to study and identify. Among the disciplines available to assess adverse health consequences of xenobiotics (‘strange’ substances in our environment), application of modern immunological methods in concert with traditional toxicologic studies have to date demonstrated significant progress in drug allergy, food allergy, environmentally induced lung diseases and autoimmunity. These successes have come from the collaboration of immunologists, allergologists, pulmonologists, pharmacologists and toxicologists. In fact, a newer discipline of immunotoxicology has emerged in order to deal with these complex issues. The National Institutes of Health, through a series of workshops and research initiatives, and in collaboration with other US government agencies, including the Environmental Protection Agency, the National Institute of Environmental Health Sciences, and the National Academy of Sciences, is attempting to foster research aimed at enhancing progress in the field of immunotoxicology. The overall aim is to encourage the use of modern immunologic approaches to the study of the alleged harmful effects of xenobiotics on the immune system. Success will permit the development of improved diagnostic tools followed by initiatives concerned with prevention. Apart from their scientific implications the results are expected to have an impact on social, legal and economic issues within society.
Role of Local IgA Antitoxin-Producing Cells for Intestinal Protection against Cholera Toxin Challenge
Authors: Lycke Nils , Bromander Anna Kari , Holmgren Jan
Published: August 2009

We examined in mice, perorally immunized with cholera toxin (CT) or cholera B subunit (CTB), the association between protection against intestinal toxin challenge and frequency and function of gut mucosal IgA antitoxin-forming cells. The in vitro production of IgA antitoxin by isolated cells and the toxin-neutralizing ability of culture supernatants were determined. Repeated oral immunizations with CT gave rise to high numbers of IgA antitoxin ‘spot-forming’ cells (SFC) in the lamina propria as well as to protection against challenge with CT in ligated intestinal loops. In contrast, mice immunized with purified CTB, gave poor IgA antitoxin SFC responses in the lamina propria and little or no protection. When a small amount of CT was used to adjuvant the response to CTB, many IgA antitoxin SFC were found; however, protection in intestinal loops remained poor. This discrepancy was explained by the predominant localization of antitoxin SFC in the proximal small intestine following oral CTB/CT-adjuvant immunization, whereas relatively few SFC were found further down in the intestine where the loop-protection test was performed. Thus, when lamina propria plasma cells were isolated from challenged loops and cultured in vitro, they released only low titers of IgA antitoxin and CT-neutralizing antibodies in culture supernatants; this was in contrast to cells from optimally immunized mice which gave supernatants with high IgA antitoxin and toxin-neutralizing antibody titers. Increasing the dose of CT, added as adjuvant to the CTB, resulted in better protection and higher numbers of IgA antitoxin SFC in more distal parts of the intestine. We also found that the build-up of strong local immunity in the gut was more dependent on repeated exposures to antigen than on immune maturation over time after oral immunizations. Our findings confirm that intestinal IgA antitoxin formation and protection against toxin challenge after oral immunization with CT are closely correlated, and that this correlation also holds true for CT-adjuvanted CTB administered by the oral route.
Kinetics and Isotype Distribution of Parasite-Specific Antibody Responses in the Spleen of Mice during Primary Infection with Schistosoma mansoni
Authors: Czerkinsky Cecil , Nilsson Lars-Åke , Ouchterlony Örjan
Published: August 2009

The solid-phase enzyme-linked immunospot assay has been adapted for enumerating cells secreting antibodies to crude antigenic extracts from the main developmental stages of Schistosoma mansoni. The frequencies of splenocytes secreting antibodies reactive with soluble antigenic extracts from cercariae, adult worms, and eggs, were examined in C57BL/6 mice during the first 12 weeks of a primary infection with S. mansoni. Despite the existence of cross-reactive moieties present in these antigenic preparations, the characteristics of the responses monitored differed with regard to kinetics, magnitude, and/or isotype distribution. The responses peaked between 8 and 10 weeks of infection, were characterized by a predominance of cells secreting IgM antibodies against all three antigens, and followed the patterns IgM > IgA > IgG for cercariae, IgM > IgG IgA for adult worms and IgM > IgG > IgA for egg extracts. On the other hand, these patterns were not always reflected in serum, expecially for cercariae-reactive circulating IgG and IgA responses. When examined for numbers of total IgM-, IgG- and IgA-producing cells, the spleen of 5. mαnsom-infected mice was shown to display considerable numbers of immunoglobulin-producing cells in all three isotypes studied. The most spectacular increases were noted for IgG-secreting cells (more than 10-fold) and for IgM-secreting cells (up to 6-fold) 4 weeks after initial cercarial exposure. Taken together, these observations indicate that primary infection with S. mansoni results in early immunoregulatory alterations which may contribute to the maintenance of specific as well as nonspecific B cell hyperactivity. The data presented in this study also suggest that the solid-phase enzyme-linked immunospot assay may have informative value in documenting the dynamic and anatomical aspects of such alterations in a variety of other tissues draining the sites of parasite migration.
Neutral Endopeptidase Modulates Tachykinin-Induced Increase in Vascular Permeability in Guinea Pig Skin
Authors: Iwamoto I. , Ueki I.F. , Borson D.B. , Nadel J.A.
Published: August 2009

To determine the regulatory role of neutral endopeptidase (NEP) in the tachykinin-induced increase in vascular permeability, we examined the effects of NEP inhibitors and of other protease inhibitors on plasma extravasation induced by intradermal injection of substance P, neurokinin A, and neurokinin B in guinea pig skin. The three tachykinins induced plasma extravasation in concentration-dependent fashions. A significant NEP activity was found to be present in the guinea pig skin. The tachykinin-induced responses were increased by the NEP inhibitors phosphoramidon and thiorphan. However, other protease inhibitors, including a kininase II inhibitor, did not affect the response. We conclude that NEP modulates the tachykinin-induced increase in vascular permeability in the skin.
Proliferation of Interleukin 2 Dependent Cytotoxic T Cell Line Cells
Authors: Gavériaux Claire , Loor Francis
Published: August 2009

Protein kinase C activators of the teleocidin family are claimed to be able to replace interleukin 2 for inducing short-term proliferation of the interleukin 2 dependent murine cytotoxic T cell line. While teleocidin B4 was found to be much more active than 12-O-tetradecanoyl-phorbol-13-acetate, a related molecule showing a substitution of a single OH by OCH3, olivoretin A, lacked detectable activity in this assay. However, the maximal proliferation achievable by protein kinase C activators did not exceed one third of the one given by recombinant interleukin 2.
Production of Interleukin-1-Alpha and -Beta by Human Peripheral Polymorphonuclear Neutrophils
Authors: Goh Kikyo , Furusawa Shuichi , Kawa Yoko , Negishi-Okitsu Shoko , Mizoguchi Masako
Published: August 2009

The mechanism of the production of interleukin-1 (IL-1) by human peripheral polymorphonuclear neutrophils (PMN) was investigated. Supernatants of PMN stimulated with 30 μg/ml lipopolysaccharide (LPS) were used as extracellular IL-1 and supernatants of their lysate as intracellular IL-1 source. IL-1 activity was measured by the C3H/HeJ thymocyte comitogenic assay. The supernatants from PMN stimulated with LPS for 72 h showed IL-1 activity which had an apparent molecular weight of 15–20 kilodaltons and pi of 5.0 and more than 8.5. It was neutralized with anti-IL-1 antibodies and it lacked IL-2 activity. Our time course study of the IL-1 assay with neutralization by anti-IL-1-alpha and -beta antibodies indicated that the extracellular IL-1-beta activity appeared predominantly in the early incubation periods, whereas alpha activity appeared predominantly in the late periods. Intracellular IL-1 -alpha but not beta activity was detected mainly at the intermediate incubation periods. These data indicate that PMN stimulated with LPS produce both IL-1-alpha and -beta, and release IL-1-beta first and IL-1 -alpha later.
Experimental Drug-Induced Allergic Nephritis Mediated by Antihapten Antibody
Authors: Joh Kensuke , Shibasaki Toshiaki , Azuma Takachika , Kobayashi Akio , Miyahara Tadashi , Aizawa Shigeo , Watanabe Naohiro
Published: August 2009

Experimental drug-induced allergic nephritis (DIAN) was mediated by an antihapten antibody. It has been postulated that DIAN is induced by cellular and humoral mechanisms. We tried to induce DIAN in mice, where the mechanism depends on humoral immunity. The first attempt was made in mice actively producing antibodies against cephem antibiotics, i.e. cephalothin (CET). Acute interstitial nephritis (AIN), morphologically similar to human disease, was obtained by injection of a CET-protein conjugate into the renal cortex in mice producing anti-CET-IgE and IgG antibodies. AIN could also be induced when normal mice, passively given anti-CET IgG antibody, received a subsequent intrarenal challenge with CET-protein conjugate. These preliminary results indicate that IgG antibody has an important role in the genesis of DIAN. Further experiments were performed with monoclonal antibodies directed against haptens instead of antibiotics in order to clarify the Ig isotype concerned. In mice passively given anti-Dansyl-IgG2a or anti-NP-IgG2a monoclonal antibodies, a challenge with an appropriate hapten-protein conjugate into the renal cortex resulted in AIN. However, transfer of anti-Dansyl-IgE or anti-DNP-IgE monoclonal antibodies, followed by challenge, did not induce AIN. In the experimental systems described, the involvement of a cellular immune mechanism is excluded. The results suggest that IgG, but not IgE antibody, is essential for the induction of DIAN by humoral immune mechanism.
Local Murine Recombinant Gamma Interferon Enhances the Acquisition of Allergic Contact Dermatitis in the Mouse
Authors: Maguire, Jr. H.C. , Guidotti M. , Weidanz W.P.
Published: August 2009

Using the model of allergic contact dermatitis in mice, we have demonstrated that local administration of recombinant (r) murine gamma interferon (γ-rIFN) to the sensitization site substantially enhances the acquisition of delayed-type hypersensitivity. Single doses of γ-rIFN from 500 to 2,000 U immunopotentiate successfully, with a suggestion of a better response at the higher doses. The immunoadjuvant effect is lost when the injections of γ-rIFN are at a site distant from the sensitization site. Kinetic studies imply that γ-rIFN is most effective when given at the time of sensitization, but significant immunopotentiation can be seen when γ-rIFN is given several days before or after sensitization.