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Mediator Release (mediator + release)
Selected AbstractsLung CD11c+ cells from mice deficient in Epstein-Barr virus-induced gene,3 (EBI-3) prevent airway hyper-responsiveness in experimental asthmaEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 6 2007Michael Hausding Abstract Epstein-Barr virus-induced gene (EBI)-3 codes for a soluble type,1 cytokine receptor homologous to the p40 subunit of IL-12 that is expressed by antigen-presenting cells following activation. Here, we analyzed the functional role of EBI-3 in a murine model of asthma associated with airway hyper-responsiveness (AHR) in ovalbumin-sensitized mice. Upon allergen challenge, EBI-3,/, mice showed less severe AHR, decreased numbers and degranulation of eosinophils and a significantly reduced number of VCAM-1+ cells in the lungs as compared to wild-type littermates. We thus analyzed lung CD11c+ cells before and after allergen challenge in these mice and found that before allergen challenge, lung CD11c+ cells isolated from EBI-3,/, mice express markers of a more plasmacytoid phenotype without releasing IFN-, as compared to those from wild-type littermates. Moreover, allergen challenge induced the development of myeloid CD11c+ cells in the lungs of EBI-3,/, mice, which released increased amounts of IL-10 and IL-12 while not expressing IFN-,. Finally, inhibition of EBI-3 expression in lung DC could prevent AHR in adoptive transfer studies by suppressing mediator release of effector cells into the airways. These results indicate a novel role for EBI-3 in controlling local immune responses in the lungs in experimental asthma. [source] Avecor Trillium Oxygenator Versus Noncoated Monolyth Oxygenator: A Prospective Randomized Controlled StudyJOURNAL OF CARDIAC SURGERY, Issue 4 2008Frédéric Vanden Eynden M.D. This study was designed to study the effects of the surface coating of a hollow fiber membrane oxygenator on coagulation, inflammation markers, and clinical outcomes. The biomaterials used to coat the membrane include heparin, polyethylene oxide chains (PEO), and sulfate/sulfonate groups. The coated membrane was compared to an uncoated oxygenator made of polypropylene. Methods: Two hundred patients who were scheduled to undergo valve repair and/or replacement surgery with or without coronary surgery were enrolled in the study. The patients were randomized to undergo CPB with either the Avecor oxygenator with TrilliumÔ (Medtronic, Minneapolis, MN, USA), a biopassive surface, or the Monolyth (Sorin, Irvine, CA, USA) oxygenator without coating. The primary and secondary endpoints were the differences between these oxygenators in regard to patients' biochemistry, coagulation profiles, inflammatory mediators, and clinical outcomes, including blood loss and neurological events. Results: There were no differences between the two groups in terms of biochemistry, coagulation profile, inflammatory mediator release, and blood loss. Five patients in the Avecor group showed clinical evidence of a stroke confirmed with computerized tomography (CT) scan imaging, and none in the noncoated oxygenator group. Conclusion: The oxygenator Avecor offers similar results in terms of inflammation and coagulation profiles and blood loss during valvular surgery compared to a standard uncoated control oxygenator. The rate of neurological events was unusually elevated in the former group of patients, with only speculative explanation at this point. Further studies are warranted to clarify this aspect. [source] Beta-2 adrenergic receptor genetic polymorphisms and asthmaJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 6 2009N. Hizawa MD Summary Beta-2-Adrenergic receptors (,2AR) participate in the physiologic responses of the lung, including bronchodilation and bronchoprotection, through mechanisms such as mucociliary clearance, fluid accumulation and mediator release from mast cells and basophils. Thus, these receptors may also play an important role in the pathophysiology of asthma. The gene encoding ,2AR (ADRB2) is extremely polymorphic, and studies of this gene improves our understanding of asthma and possibly lead to new methods to prevent, diagnose and treat it. This review summarizes results from various studies on the possible relationship of ADRB2 polymorphisms to asthma and asthma-related phenotypes, including bronchodilator responses to inhaled ,2 -agonists. At present, it appears that, for asthma, ADRB2 polymorphisms are not aetiologically involved. However, they might affect disease severity and clinical response to both acute and chronic administration of ,2 -agonists. The development is that by assessing the ADRB2 genotype, it might be possible to predict the clinical course of asthma as well as responsiveness to chronic administration of ,2 -agonists. Carefully, performed and adequately powered clinical trials continue to be important for achieving those goals. [source] Macrophage exposure to particulate titanium induces phosphorylation of the protein tyrosine kinase lyn and the phospholipases C,-1 and C,-2JOURNAL OF ORTHOPAEDIC RESEARCH, Issue 3 2002Phillip L. Palmbos A frequent long-term complication of total joint arthroplasty is aseptic loosening, the end result of wear debris production, synovial macrophage activation, inflammatory mediator release, and osteolysis about the implant,bone or cement,bone interface. To elucidate the mechanisms of particle-induced macrophage activation and mediator production, we studied early signal transduction events using J774A.1 macrophages and 3 ,m titanium particles. Treating macrophages with herbimycin A or genistein, two inhibitors of protein tyrosine kinases (PTKs), inhibited titanium phagocytosis as well as secretion of tumor necrosis factor-, (TNF-,) and prostaglandin-E2 (PGE2) in a dose-dependent manner. Both processes therefore depend on a PTK signaling cascade. Specifically, macrophage exposure to titanium-induced phosphorylation of multiple proteins including the Src kinase Lyn and phospholipase C,-1 and C,-2. Phosphorylation peaked within 2 min and returned to baseline within 45 min. Similar but not identical phosphorylation patterns were obtained when cells were stimulated with titanium preincubated with serum or albumin, suggesting distinct signal transduction pathways dependent on particle coating. © 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved. [source] Fructus Ligustrum lucidi inhibits inflammatory mediator release through inhibition of nuclear factor-,B in mouse peritoneal macrophagesJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 9 2007Hyo-Jin An ABSTRACT Fructus Ligustrum lucidi (FLL) is a widely used herbal medicine for the treatment of a variety of pathologies. We have investigated the anti-inflammatory mechanism of FLL in mouse peritoneal macrophages. FLL exerted an anti-inflammatory action through inhibition of lipopolysaccharide (LPS)-induced tumour necrosis factor (TNF)-, production in mouse peritoneal macrophages. The maximal inhibition rate of TNF-, production by FLL (0.5 mg mL,1) was 60.88 + 0.30%. In the inflammatory process, nitric oxide (NO) and prostaglandin E2 (PGE2) increased in peritoneal macrophages. FLL decreased the protein level of NO and PGE2 in LPS-stimulated mouse peritoneal macrophages. In addition, FLL inhibited nuclear factor-,B activation and I,B-, degradation by the decrease in I,B-, phosphorylation. Our study suggested that FLL reduced inflammation via an important molecular mechanism, which might explain its beneficial effect in the regulation of inflammatory reactions. [source] Interstitial Cystitis and the Therapeutic Effect of Suplatast TosilateLUTS, Issue 2009Yukio HAYASHI Painful bladder syndrome (PBS)/interstitial cystitis (IC) can be a chronic and debilitating disease characterized by urinary urgency, frequency, and bladder pain, which are often very difficult to treat, regardless of currently-proposed treatments. Suplatast tosilate (IPD-1151T) is an immunoregulator that suppresses Th2 cytokine production, immunoglobulin E (IgE) synthesis, chemical mediator release from mast cells, and eosinophilic recruitment. In a preliminary, open-label clinical study of IPD-1151T in 14 women with IC, treatment with IPD-1151T significantly increased bladder capacity and decreased urinary urgency, urinary frequency, and lower abdominal pain, as measured by the IC symptom index, in patients with non-ulcerative IC. A concomitant reduction in immunological parameters (eosinophils, IgE, and urine T cells) was observed. Also, in basic experimental studies using hydrochloric acid-induced chronic cystitis rats, the oral administration of IPD-1151T (0.1,100 mg/kg/day) for 7 days after the induction of cystitis dose dependently increased the intercontraction intervals and micturition volume. In addition, the infiltration of mast cells and eosinophils into the bladder was suppressed by IPD-1151T. These findings suggest that IPD-1151T could be a new medicine for treating debilitating symptoms, such as bladder pain and urinary frequency in PBS/IC. [source] Immunologic characterization of isoforms of Car b 1 and Que a 1, the major hornbeam and oak pollen allergensALLERGY, Issue 3 2009M. Wallner Background:, Birch pollen allergy is one of the most common causes of spring pollinosis often associated with hypersensitivity reactions to pollen of other Fagales species. Yet, only the major disease eliciting allergens of alder and hazel have been fully characterized. Therefore, the aim of this study was to perform cloning, expression and immunologic characterization of the Bet v 1 homologues from oak (Que a 1) and hornbeam (Car b 1). Methods:, The isoform pattern of Car b 1 and Que a 1 was analyzed by proteomics using 2D gel electrophoresis and LC ESI-QTOF MS. Isoallergens showing high IgE-binding were cloned and expressed in Escherichia coli. IgE-binding activity of the recombinant proteins was determined by enzyme-linked immunosorbent assay (ELISA) and basophil mediator release assays using serum samples from patients mainly exposed either to oak and hornbeam or to birch pollen. Cross-reactivity of the allergens was further investigated at the T-cell level. Results:, Dominant isoforms of Car b 1 and Que a 1, identified by mass spectrometry, showed different IgE-binding properties when testing Fagales pollen-allergic patients living in birch-free areas as compared to birch-sensitized individuals. Conclusion:, Tree pollen-allergic patients who are primarily exposed to Fagales pollen other than birch reacted stronger with rCar b 1 and rQue a 1 than with rBet v 1, as determined by inhibition ELISA and basophil mediator release assays. Thus, rCar b 1 and rQue a 1 allergens should be considered for improving molecule-based diagnosis and therapy of tree pollen allergies manifesting in birch-free areas. [source] AllergoOncology: the role of IgE-mediated allergy in cancerALLERGY, Issue 10 2008E. Jensen-Jarolim Epidemiological studies have suggested inverse associations between allergic diseases and malignancies. As a proof of concept for the capability of immunoglobulin E (IgE) to destruct tumor cells, several experimental strategies have evolved to specifically target this antibody class towards relevant tumor antigens. It could be demonstrated that IgE antibodies specific to overexpressed tumor antigens have been superior to any other immunoglobulin class with respect to antibody-dependent cellular cytotoxicity (ADCC) and phagocytosis (ADCP) reactions. In an alternative approach, IgE nonspecifically attached to tumor cells proved to be a powerful adjuvant establishing tumor-specific immune memory. Active Th2 immunity could also be achieved by applying an oral immunization regimen using mimotopes, i.e. epitope mimics of tumor antigens. The induced IgE antibodies could be cross-linked by live tumor cells leading to tumoricidic mediator release. Thus, IgE antibodies may not only act in natural tumor surveillance, but could possibly also be exploited for tumor control in active and passive immunotherapy settings. Thereby, eosinophils, mast cells and macrophages can be armed with the cytophilic IgE and become potent anti-tumor effectors, able to trace viable tumor cells in the tissues. It is strongly suggested that the evolving new field AllergoOncology will give new insights into the role of IgE-mediated allergy in malignancies, possibly opening new avenues for tumor therapy. [source] Sinus CT scans and mediator release in nasal secretions after nasal challenge with cypress pollensALLERGY, Issue 8 2004V. Piette Background:, Involvement of paranasal sinuses has been suggested in allergic rhinitis but not clearly demonstrated. Aims:, To investigate the relationship between intermittent allergic rhinitis and computerized tomography (CT). Methods:, Twenty patients with intermittent rhinitis and sensitized to cypress pollens underwent unilateral nasal provocation tests (NPTs) using increasing concentrations of cypress pollens out of the pollen season. Sinus CT-scans were carried out just before a NPT and 24 h later. Nasal lavage was carried out just before a NPT, 30 min after a positive challenge and again 24 h later. Leucotriene C4/D4, intracellular adhesion molecule-1 and eosinophil cationic protein were measured in nasal secretions. Results:, Thirteen patients (65%) showed an alteration in their CT-scans after allergen challenge. Ten of them showed sinus changes controlateral to their allergenic provocation. Radiological changes mainly affected the osteomeatal complex and the ethmoid sinuses. Pre-existing abnormalities (13 of 20 cases) mainly concerned the maxillary sinuses. There was no correlation between CT-scan abnormalities and levels of mediators released in nasal secretions. Conclusions:, We have shown that nasal allergen challenge can produce radiological changes in the paranasal sinuses. This mainly concerned the ethmoid sinuses. [source] Tomato profilin Lyc e 1: IgE cross-reactivity and allergenic potencyALLERGY, Issue 5 2004S. Westphal Background:, To date, very little data are available about the nature of tomato allergens. Immunoglobulin E (IgE) cross-reactive profilins have been suggested to account for allergic symptoms in patients suffering from tomato allergy. Methods:, The cDNA of tomato profilin was amplified by reversely transcribed polymerase chain reaction (RT-PCR) from total RNA extracted from ripe tomato fruit. The gene was cloned into the pET101D expression plasmid and the protein was produced in Escherichia coli BL21. Purification was performed via poly- l -proline (PLP) affinity chromatography. IgE reactivity of recombinant tomato profilin was investigated by immunoblot and enzyme-linked immunosorbent assay. IgE-inhibition studies were performed to analyse cross-reactivity with other profilins. To determine the allergenic activity of the recombinant protein, basophil histamine release assays using sera of patients with adverse reactions to tomato were performed. Results:, Profilin was identified as a new minor allergen in tomato fruits. The recombinant tomato profilin comprises 131 amino acids and high sequence identity to other allergenic food and pollen profilins. It was shown to be IgE-reactive with a prevalence of 22% (11/50) in tomato-allergic patients. In patients with tomato allergy and multiple sensitization to other foods and birch pollen, IgE directed against tomato profilin showed a strong cross-reactivity with profilins from plant food sources and birch pollen. The tomato profilin was able to induce mediator release from human basophils. Conclusion:, The tomato profilin is a minor allergen in tomato fruit. Thus, it shows biological activity, as confirmed by in vitro histamine release assays with human basophils and thereby has the potential to account for clinical symptoms in tomato-allergic patients. [source] Characterization of IgE responses in a rodent model of filariasis and the allergenic potential of filarial antigens using an in vitro assayPARASITE IMMUNOLOGY, Issue 1 2003Susanne Hartmann SUMMARY Filarial infections are characterized by high IgE antibody responses. So far, it is not clear whether IgE antibodies are involved in protection, pathology or both. We established a bioassay to detect reactive IgE antibodies in jirds infected with the filaria Acanthocheilonema viteae. Sera of A. viteae -infected jirds were used to sensitize rat basophil leukaemia (RBL) cells and degranulation was stimulated by addition of antigens of A. viteae. Reactive IgE responses were detected from 2 weeks post infection (p.i.) and throughout the A. viteae infection. Male antigen triggered the strongest mediator release, followed by female worms, infective larvae (L3) and microfilariae. Separation of male and female antigen indicated that several antigens of both genders are potent allergens. In particular, one male specific allergen of about 550 kDa induced strongest degranulation of RBL cells. In addition, mediator release stimulated by antigen fractions of about 15 kDa was due to filarial cystatin. In conclusion, we describe a convenient in vitro assay to examine IgE mediated responses in jirds. A sex specific filarial protein with high allergenic potential is identified and cystatin is established as a potent allergen of A. viteae. [source] Antiallergic and antihistaminic effect of two extracts of Capparis spinosa L. flowering budsPHYTOTHERAPY RESEARCH, Issue 1 2005Domenico Trombetta Abstract The antiallergic properties of two lyophilized extracts obtained from Capparis spinosa L. flowering buds (capers) by methanol extraction, carried out at room temperature (CAP-C) or with heating at 60 °C (CAP-H), were investigated. The protective effects of CAP-H and CAP-C, orally administered (14.28 mg[sol ]kg), were evaluated against Oleaceae antigen challenge-induced and histamine-induced bronchospasm in anaesthetized guinea-pigs. Furthermore, the histamine skin prick test was performed on humans, applying a gel formulation containing 2% CAP-C (the only extract able to protect against histamine-induced bronchospasm) on the skin for 1 h before histamine application and monitoring the erythema by reflectance spectrophotometry. The CAP-H showed a good protective effect against the bronchospasm induced by antigen challenge in sensitized guinea-pigs; conversely, a significant decrease in the responsiveness to histamine was seen only in CAP-C pretreated animals. Finally, the CAP-C gel formulation possessed a marked inhibitory effect (46.07%) against histamine-induced skin erythema. These two caper extracts displayed marked antiallergic effectiveness; however, the protective effect of CAP-H was very likely due to an indirect mechanism (for example, inhibition of mediator release from mast cells or production of arachidonic acid metabolites); conversely, CAP-C is endowed with direct antihistaminic properties. The different mechanisms of action of CAP-H and CAP-C may be related to a difference in the extraction procedure and, thus, in their qualitative[sol ]quantitative chemical profile. Copyright © 2005 John Wiley & Sons, Ltd. [source] Potentiation of Histamine Release by Microfungal (1,3)- and (1,6)-,-D-GlucansBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 6 2007Peter Holck The mechanisms by which they induce these effects are, however, not clear. In the present study, mediator release and its potentiation by the (1,3)-,-D-glucan as well as by the (1,6)-,-D-glucan found in yeast and other fungi were therefore examined. Blood leucocytes from healthy volunteers and from patients allergic to house dust mite were incubated with (1,3)-,-D-glucans with increasing 1,6-branchings: curdlan [a linear (1,3)-,-D-glucan], laminarin and scleroglucan, and furthermore with pustulan, a linear (1,6)-,-D-glucan. Histamine release was not observed on exposure to the glucans only, but in the presence of anti-immunoglobulin E (IgE) antibody or specific antigens, all the glucans investigated led to an enhancement of the IgE-mediated histamine release. The glucans induced a significant potentiation of the mediator release when present at concentrations in the range of 2,5 × 10,5 M. These results suggest that (1,3)-,-D-glucan as well as (1,6)-,-D-glucan aggravates IgE-mediated histamine release. Knowledge concerning the effects of glucans on immune responses may be of importance for understanding and treating inflammatory and allergic diseases. [source] Polyphenol-enriched apple extract attenuates food allergy in miceCLINICAL & EXPERIMENTAL ALLERGY, Issue 6 2010A. W. Zuercher Summary Background The immune system may be modulated with nutrition to prevent the development or to treat the symptoms of allergy. Among other foods, consumption of apples has been linked to reduced incidence of atopic dermatitis and respiratory allergy. Objective We evaluated the efficacy and mechanisms of a polyphenol-enriched apple extract in reducing symptoms of food allergy. Methods In a model of food allergy to ovalbumin (OVA), BALB/c mice were fed with an apple extract either during sensitization or just before the challenge. After the challenge, allergic symptoms were scored, OVA-specific serum immunoglobulins were determined by ELISA, cytokine production by mesenteric lymph node (MLN) cells was measured by a multiplex assay and gene expression profiles in the intestine were addressed using quantitative real-time PCR. Results Consumption of the apple extract reduced symptoms of food allergy upon challenge. This was paralleled by reduced levels of intestinal mast cell protease, diminished cytokine secretion by MLN cells and reduced local intestinal mRNA expression of various T-helper type-2 associated and pro-inflammatory genes. Mechanistic studies suggested decrease of mediator release by effector cells and reduction of allergenicity by protein,polyphenol interaction as potential mechanisms responsible for protection. Conclusion Polyphenol-enriched apple extract can attenuate food allergy symptoms in sensitized mice via two distinct possible mechanisms. [source] Nasal challenges with recombinant derivatives of the major birch pollen allergen Bet v 1 induce fewer symptoms and lower mediator release than rBet v 1 wild-type in patients with allergic rhinitisCLINICAL & EXPERIMENTAL ALLERGY, Issue 10 2002M. Van Hage-Hamsten Summary Background Genetic engineering of the major birch pollen allergen (Bet v 1) has led to the generation of recombinant Bet v 1 derivatives with markedly reduced IgE-binding capacity, but with retained T cell activating ability. Objective To compare the mucosal reactivity to rBet v 1 derivatives with rBet v 1 wild-type as basis for new therapeutic strategies for birch pollen allergy based on mucosal tolerance induction. Methods Outside the pollen season, 10 patients with birch pollen allergic rhinitis and mild asthma underwent four nasal challenge-sessions in a randomized, double-blind, and cross-over design, employing increasing doses of rBet v 1 fragment mix, rBet v 1 trimer, rBet v 1 wild-type and diluent (albumin). Nasal lavage fluids (NAL) were collected before the challenge-series as well as 10 min, 4 and 24 h thereafter. Nasal lavage fluid levels of tryptase as well as EPO and ECP were measured as indices of mast cell and eosinophil activity, respectively. Results All 10 patients tolerated the highest accumulated dose, 8.124 µg, when challenged with rBet v 1 trimer, eight with rBet v 1 fragments compared to one when challenged with rBet v 1 wild-type. No late phase reactions were observed. The change in tryptase levels (pre-challenge vs. 10 min) was significantly lower after challenges with rBet v 1 trimer and rBet v 1 fragments than with rBet v 1 wild-type. The change in EPO/ECP concentration pre-challenge versus 4 h post-challenge was lower for rBet v 1 trimer and the change was significantly lower when pre-challenge versus 24 h post-challenge to rBet v 1 fragments and rBet v 1 wild-type was examined. Conclusion The derivatives induced significantly fewer symptoms and lower mast cell and eosinophil activation than rBet v 1 wild-type upon application to the nasal mucosa. They could in the future be candidates for immunotherapy based on mucosal tolerance induction. [source] Blockade of superoxide generation prevents high-affinity immunoglobulin E receptor-mediated release of allergic mediators by rat mast cell line and human basophilsCLINICAL & EXPERIMENTAL ALLERGY, Issue 4 2002T. Yoshimaru Summary Background Previous studies have shown that rat peritoneal mast cells and mast cell model rat basophilic leukaemia (RBL-2H3) cells generate intracellular reactive oxygen species (ROS) in response to antigen challenge. However, the physiological significance of the burst of ROS is poorly understood. Objective The present study was undertaken to investigate the role of superoxide anion in mediator release in rat and human cell systems. Methods RBL-2H3 cells were directly stimulated with anti-rat Fc,RI ,-subunit monoclonal antibody (mAb). For the analysis of human cell system, leucocytes were isolated by dextran sedimentation from healthy volunteers or from patients, and challenged either with anti-human Fc,RI mAb or with the relevant antigens. Superoxide generation was determined by chemiluminescence-based methods. The releases of histamine and leukotrienes (LT)s were determined by enzyme-linked immunosorben assay (ELISA). Results Cross-linking of Fc,RI on RBL-2H3 cells or on human leucocytes from healthy donors by the anti-Fc,RI mAb resulted in a rapid generation of superoxide anion, as determined by chemiluminescence using superoxide-specific probes. Similarly, leucocytes from patients generated superoxide anion in response to the challenge with the relevant allergen but not with the irrelevant allergen. Furthermore, diphenyleneiodonium (DPI), a well-known inhibitor of flavoenzymes suppressed the superoxide generation and the release of histamine and LTC4 induced by the anti-Fc,RI mAb or by allergen in parallel. Conclusion These results indicate that both RBL-2H3 cells and human basophils generate superoxide anion upon Fc,RI cross-linking either by antibody or by allergen challenge and that blockade of the generation prevents the release of allergic mediators. The findings strongly support the role of superoxide generation in the activation of mast cells and basophils under both physiological and pathological conditions. The findings suggest that drugs regulating the superoxide generation have potential therapeutic use for allergic disorders. [source] Matrix proteins and eosinophil mediator releaseCLINICAL & EXPERIMENTAL ALLERGY, Issue 6 2000Wardlaw No abstract is available for this article. [source] Superallergens: a novel mechanism of IgE-mediated activation of human basophils and mast cellsCLINICAL & EXPERIMENTAL ALLERGY REVIEWS, Issue 2004G. Marone Summary Here we report that specific proteins induced in vivo by viruses (e.g. protein Fv), viral proteins (e.g. gp120) or bacterial proteins (e.g. protein L and protein A) can activate human mast cells and basophils (Fc,RI+ cells) to release proinflammatory mediators and cytokines, thereby functioning as immunoglobulin superallergens. Protein Fv acts as an endogenous immunoglobulin superallergen by interacting with IgE VH3+. Similarly, gp120 of HIV-1 is a viral superallergen activating Fc,RI+ cells through interaction with IgE VH3+. Protein A of Staphylococcus aureus functions by interacting with IgE VH3+. Finally, Peptostreptococcus magnus, protein L and a fragment denoted B1,B4 induce mediator release from Fc,RI+ cells through interaction with , light chains of IgE bound on human Fc,RI+ cells. Thus, we have identified a novel mechanism by which endogenous, bacterial and viral proteins specifically activate Fc,RI+ cells, thereby acting as immunoglobulin superallergens. The in vivo implications of IgE-mediated activation of human Fc,RI+ cells by these immunoglobulin superallergens have yet to be defined. However, it is not inconceivable that endogenous, bacterial and viral superallergens play a pathophysiological role in certain forms of allergic reactions. [source] | |||||||||||||||||||||||||