Inhibition of anaphylactic histamine release and pulmonary distress in rats by nonspecific IgE

Myeloma IgE, obtained from ascitic fluid of rats previously inoculated with the IgE-producing cell line IR-162, was administered in prophylactic and therapeutic regimens to rats passively and actively sensitized to ovalbumin. Administration of myeloma IgE prior to passive sensitization resulted in approximately 95% inhibition of anaphylactic histamine release and significant protection from anaphylactic pulmonary distress. Myeloma IgE treatment prior and subsequent to active sensitization brought about a 70-80% inhibition of anaphylactic histamine release. A similar pattern of protection was seen in animals that received 5 but not 3 weekly myeloma IgE treatments subsequent to active sensitization. These findings indicate that treatment with nonspecific IgE prior to sensitization is effective in blocking anaphylactic reactions but competition with cell-bound IgE in sensitized animals requires prolonged administration of relatively large quantities of 'nonsense' IgE.     

In vitro reversed anaphylaxis: characteristics of anti-IgE mediated histamine release

Leucocytes from allergic and most normal human donors release histamine when challenged with antibodies against human γ-globulin. This reaction (reversed in vitro anaphylaxis) is due primarily to anti-IgE antibodies although there is some response in most donors to antisera against IgG even after it has been absorbed with light and ε chains. The anti-IgE is, however, several 100-fold more potent than the anti-IgG. By passive sensitization of the leucocytes of a normal donor with serum from a ragweed-allergic patient it was shown that the normal cells became sensitive to anti-IgE and ragweed antigen E at the same time; in both cases, there was an inverse relationship between the serum concentration used for passive sensitization and the concentration of antigen or antibody required for histamine release. There is a rough correlation (r_s = 0.42; P<0.01) between the serum IgE concentration and the response of leucocytes from allergic donors to anti-IgE and an excellent correlation (r_s = 0.82; P<0.01) between the response of the cells to ragweed antigen E and anti-IgE. There is also a strong parallel between the mechanism of direct, antigen mediated histamine release and the reversed reaction induced by anti-IgE. Both appear to be non-serum requiring, non-cytotoxic, secretory-like responses which are inhibited by theophylline, cyclic AMP and colchicine. These data suggest that cell bound IgE is of major importance in the in vitro anaphylactic response and that the direct and reversed in vitro anaphylactic reactions both operate through cell-bound IgE and share a common reaction mechanism.     

Mechanism of histamine release from rat isolated peritoneal mast cells by dextran: The role of immunoglobulin E

In vivo passive sensitization of rat peritoneal mast cells withNippostrongylus braziliensis antiserum or rat monoclonal myeloma IgE greatly enhanced histamine releasein vitro by dextran or anti IgE, but did not alter release by compound 48/80 or A23187. Conversely, removal of IgE from the cells by acid pH abolished histamine release by dextran and anti IgE but did not impair release by compound 48/80. Whereas, histamine release from cells isolated from rats genetically resistant to dextran (NR rats) by anti IgE was potentiated by passive sensitization, dextran was unable to stimulate secretion from control or sensitized NR cells. The results suggest that dextran releases histamine by interaction with cell-fixed IgE and that the NR mast cell membrane lacks the ability to interpret this stimulus.     

Immunologic histamine release in vitro from the heart and lung of the cynomolgus monkey

Immunologic histamine release was evoked from the sensitized fragmented cardiac and pulmonary tissue of the cynomolgus monkey by a reverse anaphylactic reaction. Ventricular and pulmonary tissue released a similar fraction (approximately 6%) of the total tissue histamine when challenged with antihuman IgE, presumably reflecting the 'active' sensitization of the monkey in vivo. Passive sensitization of these tissues in vitro resulted in significantly greater immunologic histamine release in 6 of the 14 ventricles and d a similar fraction (approximately 6%) of the total tissue histamine when challenged with antihuman IgE, presumably reflecting the 'active' sensitization of the monkey in vivo. Passive sensitization of these tissues in vitro resulted in significantly greater immunologic histamine release in 6 of the 14 ventricles and d a similar fraction (approximately 6%) of the total tissue histamine when challenged with antihuman IgE, presumably reflecting the 'active' sensitization of the monkey in vivo. Passive sensitization of these tissues in vitro resulted in significantly greater immunologic histamine release in 6 of the 14 ventricles and in the lungs. The antiallergic compounds, disodium cromoglycate and SK&F 64398, inhibited immunologic histamine release from passively sensitized monkey ventricular tissue. These results demonstrate that ventricular histamine may be immunologically released and that this release process can be pharmacologically inhibited in a manner similar to that of pulmonary tissue.     

Allergy to suxamethonium: persisting abnormalities in skin tests, specific IgE antibodies and leucocyte histamine release

Twenty-one patients, who had previously experienced an anaphylactic reaction to suxamethonium during general anaesthesia, were selected for this study. Initially, skin tests with muscle relaxants were carried out in the twenty-one patients, detection of specific anti-choline IgE in nineteen, and leucocyte histamine release in seventeen. These three tests were then repeated between 1 year and 4 years after the initial evaluation. In the majority of patients, sensitization to the muscle relaxants persisted for more than 1 year after the anaphylactic reaction. Only three patients out of twenty-one (4%) had negative skin tests when retested 1–4 years later. A reduction in leucocyte histamine release was noticed in one of the seventeen retested patients (6%). Modifications of anti-choline IgE were observed in five of nineteen patients (26%). The persistence of sensitization to suxamethonium may result from repeated stimulation by occasional contacts with quaternary ammonium compounds. This study demonstrates the reliability of skin tests, leucocyte histamine release and detection of anti-choline IgE to diagnose allergic reactions to suxamethonium, even when they are performed a long time after the initial anaphylactic reaction.     

Asthma due to the complex salts of platinum—a cross-sectional survey of workers in a platinum refinery

Anamnestic and immunological data of workers of a platinum refinery (group A: workers with work-related symptoms, n= 8; group B: workers with symptoms not clearly work-related, n= 9; group C: asymptomatic workers, n= 13) and controls (group D: atopies, n= 10; group E: non-atopics, n= 16) were compared. Exposure to platinum salt was higher in group A than in groups B or C. In group A, symptoms developed 4 months (median) after the onset of exposure. All subjects of group A and three workers of group B, but none of the workers of the other groups, showed a positive cutaneous reaction to (PtCl₆)^2?. Total serum IgE was higher in groups A and D than in groups B, C or E.(PtCl₆)^2?-specific IgE was higher in group A, but there was non-specific binding of (PtCl₆)^2? to IgE. Histamine release with (PtCl₆)^2? was found in all groups and was highest in atopic controls. Histamine release with (PtCl₆)^2? and histamine release with anti-IgE showed an excellent correlation, suggesting a similar release mechanism of (PtCl₆)^2? and anti-IgE. In skin-test positive subjects, high cutaneous (PtCl₆)^2?-sensitivity is linked to high histamine release with (PtCl₆)^2? or anti-IgE, supporting the concept of a role of cell surface IgE or IgE-Fc-receptor in the release process with platinum salts. However, high specificity of cutaneous reactions contrasts with low specificity of in-vitro tests with (PtCl₆)^2?. A different reaction of basophils and mast cells, when challenged with free platinum salts, is hypothesized. We conclude that neither histamine release from basophils with (PtCl₆)^2? nor RAST for the detection of (PtCl₆)^2? specific IgE are helpful in the diagnosis of platinum salt allergy.     

Bronchial allergen challenge in subjects with low levels of allergic sensitization to indoor allergens

BACKGROUND: Low skin reactivity to common inhalant allergens is frequently found in asymptomatic individuals as well as in patients with respiratory complaints. However, most studies on bronchial allergen challenge concern patients with high levels of allergic sensitization. The present study was directed to bronchial reactions after allergen challenge in subjects with low skin reactivity to Dermatophagoides pteronyssinus or cat dander. METHODS: Titrated intracutaneous skin tests, skin prick tests, specific IgE assays, histamine release on washed leukocytes, and bronchial histamine and allergen-challenge tests were performed in 20 subjects with an intracutaneous skin test threshold for cat dander (Felis domesticus) or D. pteronyssinus above 0.1 BU/ml (mean wheal diameter in skin prick test with 10000 BU/ml: 4.4mm). Ten of the 20 patients had specific IgE below the detection limit in at least one of the three IgE assays which were done. Fifteen patients had a specific IgE level below 2 kU/I in all three tests. As a positive control group, the same parameters were studied in seven moderately sensitized patients with an intracutaneous skin test threshold below 0.1 BU/ml (mean wheal diameter with 10000 BU/ml: 7.2mm). RESULTS: The 20 subjects with low levels of allergic sensitization had an early decrease in FEV1 of 8.6% (P<0.01) and a mean late decrease of 6.3% (P<0.05). There was a trend for decrease in PC20 histamine 24h after allergen challenge (-0.4 doubling doses, P=0.09). CONCLUSIONS: In this group of subjects with low levels of allergic sensitization, a statistically significant early and late decrease in FEV1 was found. However, the decrease in lung function was small and unnoticed by most patients. The increase in nonspecific bronchial hyperresponsiveness after bronchial allergen challenge did not reach statistical significance in the study group. The results indicate that allergen exposure in patients with low levels of allergic sensitization may lead to airways changes in the absence of acute symptoms.     

Bronchial histamine reactivity: its relationship to the reactivity of the bronchi to allergens

The aim of this study was to examine the proposal that the magnitude of the response of the bronchi to an immediate allergic reaction depends not only on the degree of sensitization of the bronchi by allergen specific IgE antibody but also on the reactivity of the bronchi to the vasoactive mediators which are released during immediate allergic reactions. This was done by determining the bronchial reactivity to Dermatophagoides pteronyssinus and to histamine of both symptomatic and asymptomatic groups of atopic subjects who had comparable serum levels of D. pteronyssinus specific IgE. Positive bronchial responses to the D. pteronyssinus extract were recorded with both the symptomatic and asymptomatic subjects, the mean bronchial threshold dose of allergen being significantly higher in the asymptomatic than in the asthmatic patients. There was a highly significant correlation between the serum level of allergen specific IgE and the bronchial threshold dose of allergen extract and also between the bronchial threshold dose of allergen extract and of histamine in all groups of subjects. The ability to predict bronchial reactivity to the allergen from the serum level of allergen specific IgE within each group was significantly better if the bronchial reactivity to histamine was included in the correlation analysis. This supports the hypothesis that whether a particular subject who is producing specific IgE antibody will develop symptoms on the inhalation of that allergen depends not only on the amount of allergen which he inhales and on the degree of sensitization of his bronchi but also on the reactivity of his bronchi to the vasoactive mediators which are released by allergen–IgE interaction.     

Saturation of immunoglobulin E (IgE) binding sites by polyclonal IgE does not explain the protective effect of helminth infections against atopy

One hypothesis for the decreased rates of atopy observed among helminth-infected individuals is that parasite-induced polyclonal immunoglobulin E (IgE) out-competes allergen-specific IgE for FcepsilonRI binding on basophils and mast cells. In experiments with fresh blood drawn from filaria-infected patients, we found no association between ratios of polyclonal to Brugia malayi antigen (BmAg)-specific IgE (range, 14:1 to 388:1) and basophil responses to BmAg as measured by histamine release. Using serum samples from a filaria-infected patient who also had dust mite (Dermatophagoides pteronyssinus)-specific IgE antibodies from time points with various ratios of polyclonal to D. pteronyssinus-specific IgE (16:1 to 86:1), we demonstrated that increased ratios of polyclonal to D. pteronyssinus-specific IgE did not attenuate basophil sensitization as measured by D. pteronyssinus-specific histamine release. Suppression of histamine release was likely not observed in either of these sets of experiments because polyclonal to antigen-specific IgE ratios were not sufficiently high, as concurrent passive sensitization of basophil experiments required ratios of polyclonal to antigen-specific IgE of greater than 500:1 to suppress basophil histamine release. Further, the intensity of IgE staining in basophil populations from 20 patients with active filaria infections correlated strongly with total serum IgE levels (rho = 0.698; P = 0.0024) with no plateau in intensity of IgE staining, even though some patients had total IgE levels of greater than 10,000 ng/ml. Our data therefore suggest that in helminth infections (and in filarial infections in particular), the ratios of polyclonal to allergen-specific IgE rarely reach those levels necessary to inhibit allergen-specific IgE-FcepsilonRI binding and to suppress allergen-induced degranulation of mast cells and basophils.     

Extraordinarily high serum IgE levels and consequences for atopic phenotypes.

BACKGROUND: IgE plays a central role in allergic diseases. Recent studies have postulated an association between serum IgE levels and bronchial asthma. OBJECTIVE: To examine the differences of atopic phenotypes in a group of individuals with extraordinarily high serum IgE levels (>10,000 kU/L) compared with children with moderately elevated IgE levels (400-1,000 kU/L). METHODS: We investigated 20 children with serum IgE levels greater than 10,000 kU/L and compared them with 56 age-matched children with serum IgE levels of 400 to 1,000 kU/L regarding prevalences of atopic dermatitis, bronchial asthma, allergic rhinoconjunctivitis, allergic sensitization, and history of anaphylaxis. RESULTS: The mean eczema severity score as determined by the Severity Scoring of Atopic Dermatitis Index was 56 vs 18 (P < 0.003), and anaphylactic reactions were reported in 20% of the group with very high serum IgE levels vs 7% in the group with moderate levels (P < 0.02). Sensitization to both aeroallergens and food allergens was detected in 80% of the group with very high serum IgE levels vs 32% of the group with moderate levels (P < 0.001). CONCLUSIONS: Our results indicate that children with very high serum IgE levels are at risk for anaphylactic reactions and more severe atopic dermatitis.     

Oral sensitization with shrimp tropomyosin induces in mice allergen-specific IgE, T cell response and systemic anaphylactic reactions

Appropriate murine models of shrimp tropomyosin (ST) allergy would be useful in investigating the mechanisms underlying food allergy in human subjects, as well as for the pre-clinical evaluation of efficacy and safety of novel therapeutic approaches. These models should mimic immune and clinical features of human disease, including anaphylactic response. We sensitized C3H/HeJ mice by the oral route with purified ST using cholera toxin (CT) as adjuvant. ST-specific IgE, IgG1, IgG2a and IgA responses were evaluated by ELISA. Spleen cell proliferation and cytokine production by allergen-specific activation were assessed. Jejunum and colon fragments were collected to evaluate the local expression of cytokine genes by PCR. Local and systemic anaphylactic reactions induced by oral ST challenge were scored according to symptoms observed. Faecal samples were collected to assess local IgA production and histamine levels. Oral sensitization with ST plus CT induced in mice significant levels of serum IgE and IgG1 and faecal IgA. ST-specific cell proliferation and IL-4, IL-13 and IFN-gamma cytokine production were induced in the spleen. After oral challenge, 100% of mice had anaphylactic symptoms while no symptoms were observed in challenged naive mice. Faecal histamine content after ST challenge appeared significantly increased in sensitized mice when compared with that observed in pre-immune mice. Jejunum mRNA expression of T(h)2 cytokines was up-regulated by ST sensitization. These results support the importance of the oral way of sensitization and of the in-depth characterization of the anaphylactic response for the development of a suitable in vivo model of food allergy.     

Regulation of in vivo IgE biosynthesis in mice with complete Freund's adjuvant

Complete Freund's adjuvant (CFA) administered before sensitization dampened the normal and cyclophosphamide-enhanced response of high and moderate IgE responder phenotype mice (CAF1 and C57B1/6J, respectively). CFA-induced suppression of IgE biosynthesis was effective in reducing anaphylactic histamine release from approximately 2,900 ng histamine per milliliter to background levels (less than 100 ng/ml). CFA-induced ascites fluid was able to reduce the cyclophosphamide-enhanced IgE response of low-responder phenotype SJL mice from 1:320 to less than 1:5 as determined by passive cutaneous anaphylaxis. Muramyl dipeptide, a mycobacterial cell wall component capable of eliciting effects similar to those seen with CFA, was shown to induce suppression of IgE production if incorporated in incomplete Freund's adjuvant. Muramyl dipeptide administered in saline was ineffective, while incomplete Freund's adjuvant alone had some immunoregulatory properties. Ongoing IgE responses were less susceptible to regulation. CFA administered to sensitized C57B1/6J mice was ineffective in inducing IgE suppression when animals were challenged with antigen.     

Genetic susceptibility to food allergy is linked to differential TH2-TH1 responses in C3H/HeJ and BALB/c mice

BACKGROUND: Although food allergy is a serious health problem in westernized countries, factors influencing the development of food allergy are largely unknown. Appropriate murine models of food allergy would be useful in understanding the mechanisms underlying food allergy in human subjects. OBJECTIVE: We sought to determine the susceptibility of different strains of mice to food hypersensitivity. METHODS: C3H/HeJ and BALB/c mice were sensitized to cow's milk (CM) or peanut by means of intragastric administration, with cholera toxin as a mucosal adjuvant. Mice were then challenged with CM or peanut. Antigen-specific IgE levels, anaphylactic symptoms, plasma histamine levels, and splenocyte cytokine profiles of these 2 strains were compared. RESULTS: CM-specific IgE levels were significantly increased only in the C3H/HeJ strain, 87% of which exhibited systemic anaphylactic reactions accompanied by significantly increased plasma histamine levels in response to challenge. BALB/c mice exhibited no significant CM-specific IgE response, increased plasma histamine levels, or anaphylactic symptoms. After peanut challenge, 100% of peanut-sensitized C3H/HeJ mice exhibited high levels of peanut-specific IgE and anaphylactic symptoms. In contrast, no hypersensitivity reactions were detected in BALB/c mice, despite the presence of significant serum peanut-specific IgE levels. Splenocytes from CM- and peanut-sensitized C3H/HeJ mice exhibited significantly increased IL-4 and IL-10 secretion, whereas splenocytes from BALB/c mice exhibited significantly increased IFN-gamma secretion. CONCLUSION: Induction of food-induced hypersensitivity reactions in mice is strain dependent, with C3H/HeJ mice being susceptible and BALB/c mice being resistant. This strain-dependent susceptibility to food allergy is associated with differential T(H)2-T(H)1 responses after intragastric food allergen sensitization.     

Allergen-sensitization in vivo enhances mast cell-induced inflammatory responses and supports innate immunity

Mast cells are immune cells that play a crucial role in inflammatory reactions related to allergic reactions and the defense against certain parasites and bacteria. In allergy, the binding of immunoglobulin E (IgE) to its high-affinity receptor (Fc?RI) sensitizes mast cells. Subsequent cross-linking of IgE-Fc?RI by multivalent antigen results in cellular activation and the release of proinflammatory mediators. Recent in vivo and in vitro experiments suggest that IgE not only acts as an allergen sensor, but also induces molecular and biological changes in mast cells. In the present study we examined whether allergen-sensitization in vivo could modify the magnitude of mast cells-induced inflammatory responses. Moreover, we studied changes in peritoneal mast cell number and histamine amount during and after sensitization. We provided evidence that sensitization, at the time of the maximum allergen-specific IgE-titer, increases the intensity of a local inflammatory process generated in a cutaneous anaphylactic reaction. Sensitization also supports innate immunity, improving survival and speeding up the resolution of an acute inflammatory reaction induced by polymicrobial sepsis, while decreasing the amount of histamine in peritoneal mast cells. In addition, our results showed that sensitization induces a late increase in the number and histamine amount of peritoneal mast cells. Thus, our findings clearly demonstrated that sensitization induces changes in mast cells which prepare the cell to induce more intense inflammatory responses. This entails an increased detrimental role in subsequent IgE-dependent allergic reactions and an improved protective function in innate defense against pathogens.     

Sensitivity to two major allergens (Cry j I and Cry j II) in patients with Japanese cedar (Cryptomeria japonica) pollinosis

Background: Japanese cedar (Cryptmeria japonica: CJ) pollinosis is one of the most important allergic diseases in Japan. Recently, the second major allergen (Cry j II) was isolated from CJ pollen. There have been no prevalence studies of sensitivity to Cry j I and Cry j II among a large number of patients with pollinosis. Objective: This study was conducted to evaluate the prevalence of sensitivity to Cry j I and Cry j II. We measured specific IgE antibodies to these allergens in the sera of 145 patients. Furthermore, comparison of the sensitivity to Cry j I and Cry j II was examined by the hisiamine release assay. Methods: Specific IgE antibodies to Cry j I and Cry j II were assayed by a fluorometric ELISA. Allergen-specific histamine release was measured by a radioimmunoassay kit, Results: More than 90% of 145 patients had specific IgE antibodies to both allergens. the remainder had specific IgE to either one or the other. There were seasonal changes in the level of specific IgE. The changes in the levels of anti-Cry j II IgE antibodies were parallel to those of anti-Cry j I IgE. The histamine release assay with leucocytes from the patients demonstrated that the allergenic potency of the two allergens is almost the same. Conclusion: Cry j II is an as important a major allergen as Cry j I.     

Keyhole limpet hemocyanin (KLH)--a potent antigen in reaginic sensitization of mice and rats; a comparison with egg albumin (EA)-induced reaction

Two distinct antigenic functions of KLH and EA were tested in four inbred strains of mice (BALB/c, 129, C3H/A, C57BL/6J:a) stimulation of reaginic antibody production after subcutaneous introduction of antigen in alum-precipitated form, and b) ability to elicit an anaphylactic reaction in vitro on pre-sensitized peritoneal mast cells. KLH was found to be more effective than EA in both functions tested, inducing higher titres of IgE and IgG1 antibody levels in the sera as well as higher percentage of histamine release from actively and passively sensitized peritoneal mast cells. Two different forms of KLH (associated and dissociated) were tested for potency in stimulating an anaphylactic sensitization of mice and rats and capacity to elicit an anaphylactic reaction on their peritoneal mast cells in vitro. In all rats as well as in BALB/c, 129 and C3H/A mice sensitization with dissociated KLH resulted in higher percentage of antigen-induced histamine release from peritoneal mast cells (an exception: mast cells of C57CL/6J mice released a little more histamine on the challenge with associated KLH). The PCA tests show, that the dissociated KLH does not act through greater stimulation of antibody formation.     

The association of lung shadowing with hypersensitivity responses in patients with allergic broncho-pulmonary aspergillosis

The levels of total serum IgE and IgE antibodies to Aspergillus fumigatus allergens were highest during an episode of symptoms associated with fresh pulmonary shadowing and a rise in the direct cosinophil count in patients with allergic bronchopulmonary aspergillosis. Agglutinin titres were greater than those found in the sera of control subjects hut did not always correlate in magnitude with total serum IgE and IgE antibody levels. The highest agglutinin titre was found in the serum of a patient with an aspergilloma in association with allergic aspergillosis. The maximum in vitro histamine release from leucocytes exposed to A. fumigatus extracts or anti-human IgE was independent of the concentration of total IgE or IgL antibodies. The leucocytes appeared to he relatively insensitive to both allergic and reverse allergic histamine release. This was considered to result from either continuous in vivo desensitization of the leucocytes by antigens shed from the fungal hyphae or, to the effect of drugs used in the treatment of (he disease, It was concluded that serial serum IgE measurements may be of value in monitoring the onset of the active phase of this disease.     

An immunological approach to the diagnosis of food sensitivity

Nineteen patients with delayed onset food sensitivity were compared with fourteen patients with immediate reactions and twenty-one non-atopic subjects in terms of clinical symptoms, foods involved and IgE mediated immunological reactions. The immediate reactors were frequently positive to all tests used: skin tests (71%), allergen induced leucocyte histamine release (71%), radioimmunodiffusion (55%) and skin window (55%). Those with the delayed onset variety were seldom positive by skin testing (13%), or skin window (0%), while 39% were positive by leucocyte histamine release and 48% demonstrated specific IgE food antibodies. Control subjects had negative responses to immunological tests for IgE antibody except for leucocyte histamine release (24%). Reasons for the differences between immediate and delayed onset food sensitivity in clinical symptoms, foods involved and immunologic parameters are discussed. A careful history in conjunction with the elimination and challenge technique remains the most useful tool at present for the delayed onset group. In vitro methods for detecting specific IgE responses may also prove to be helpful.     

Inhibition of Immunologic and Nonimmunologic Stimulation-Mediated Anaphylactic Reactions by the Aqueous Extract of Mentha arvensis

The effect of aqueous extract of Mentha arvensis L. var. piperascens Malinv. (Labiatae) (MAAE) on immunologic and nonimmunologic stimulation-mediated anaphylactic reactions was studied. Nonimmunologic anaphylactic reaction was induced by compound 48/80 injection. MAAE (0.005 to 0.5 g/kg) inhibited systemic anaphylactic reaction induced by compound 48/80. Immunologic anaphylactic reaction was generated by sensitizing the skin with anti-dinitrophenyl (DNP) IgE followed 48 h later with an injection of antigen. MAAE (0.001 to 1 g/kg) dose-dependently inhibited passive cutaneous anaphylaxis (PCA) when intraperitoneally, intraveneously and orally administered. MAAE (0.001 to 1 mg/ml) dose-dependently inhibited the histamine release from rat peritoneal mast cells (RPMC) activated by compound 48/80 or anti-DNP IgE. Moreover, MAAE (0.1 mg/ml) had a significant inhibitory effect on anti-DNP IgE-mediated tumor necrosis factor-α (TNF-α) production. These results indicate that MAAE inhibits immunologic and nonimmunologic stimulation-mediated anaphylactic reactions and TNF-α production from RPMC.     

Inhibition of anaphylactic histamine releasein vitro by GABA

Inhibitory effect of GABA on anaphylactic histamine releasein vitro is not mimicked by 2-aminoethansulphonic acid (taurine), an aminoacid unrelated to GABA neurotransmission.Tetrodotoxin (TTX) 6×10^–7 M, a concentration known to block neuronal mechanism but not to modify muscle membrane and anaphylactic histamine release, strongly prevented the inhibition caused by GABA in the Schultz-Dale reaction and in anaphylactic histamine release.The inhibitory effect of GABA on anaphylactic reactionin vitro thus appears to be specific for this aminoacid and is neurogenic in nature, in that it requires integrity of neuronal mechanisms.