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Investigation of the endogenous chemoattractants involved in 111 In‐eosinophil accumulation in passive cutaneous anaphylactic reactions in the guinea‐pig
Author(s) -
Weg Vivian B.,
Watson Malcolm L.,
Faccioli Lucia H.,
Williams Timothy J.
Publication year - 1994
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1994.tb16170.x
Subject(s) - endogeny , guinea pig , eosinophil , chemotaxis , immunology , anaphylactic reactions , chemistry , biology , allergy , asthma , biochemistry , anaphylaxis , endocrinology , receptor
1 Eosinophil accumulation and plasma extravasation are features of type I allergic responses. In an attempt to characterize the mediators of these responses, we have examined the local accumulation of 111 In‐eosinophils and leakage of 125 I‐human serum albumin ( 125 I‐HSA) during passive cutaneous anaphylaxis (PCA) reactions and in response to defined inflammatory mediators in the guinea‐pig. Animals were passively sensitized by intradermal injection of anti‐bovine gamma globulin antibody (50 μl, 1/50 dilution). After 20–24 h, animals were injected intravenously with 111 In‐eosinophils and 125 I‐HSA for the measurement of cell accumulation and plasma leakage, respectively. 2 When injected into sensitized sites, antigen caused a dose‐related increase in the accumulation of 111 In‐eosinophils and plasma leakage in guinea‐pig skin. Time course experiments over 24 h revealed that the maximal rate of 111 In‐eosinophil accumulation occurred over the first 90 min, with little accumulation at later time points. Plasma leakage was completed within the first 30 min after challenge. Responses to the mast cell degranulator, compound 48/80, exhibited very similar responses to the PCA reaction. 3 Co‐injection of antigen with the PAF antagonist, WEB 2086 (10 −7 mol/site) or the 5‐lipoxygenase inhibitor, PF 5901 (10 −7 mol/site) did not significantly alter the accumulation of 111 In‐eosinophils or plasma leakage, whereas these drug doses abolished responses to exogenous PAF (10 −9 mol/site) and arachidonic acid (AA, 3 × 10 −8 mol/site), respectively. The H 1 receptor antagonist chlorpheniramine (2.5 × 10 −8 mol/site) did not reduce antigen‐induced 111 In‐eosinophil accumulation. Drug combinations were also injected with antigen into sensitized sites, but were unable to reduce 111 In‐eosinophil accumulation. 4 These results indicate that anaphylactic eosinophil accumulation in this model involves mediators other than histamine, PAF or lipoxygenase products. This is in contrast to plasma leakage in this reaction, which can be abolished by a combination of antagonists blocking these mediators.