INVESTIGATION OF THE ENDOGENOUS CHEMOATTRACTANTS INVOLVED IN IN-111-EOSINOPHIL ACCUMULATION IN PASSIVE CUTANEOUS ANAPHYLACTIC REACTIONS IN THE GUINEA-PIG

1 Eosinophil accumulation and plasma extravasation are features of typ e I allergic responses. In an attempt to characterize the mediators of these responses, we have examined the local accumulation of In-111-eo sinophils and leakage of I-125-human serum albumin (I-125-HSA) during passive cutaneous anaphylaxis (PCA) reactions and in response to defin ed inflammatory mediators in the guinea-pig. Animals were passively se nsitized by intradermal injection of anti-bovine gamma globulin antibo dy (50 mu l, 1/50 dilution). After 20-24 h, animals were injected intr avenously with In-111-eosinophils and I-125-HSA for the measurement of cell accumulation and plasma leakage, respectively. 2 When injected i nto sensitized sites, antigen caused a dose-related increase in the ac cumulation of In-111-eosinophils and plasma leakage in guinea-pig skin . Time course experiments over 24 h revealed that the maximal rate of In-111-eosinophil accumulation occurred over the first 90 min, with li ttle accumulation at later time points. Plasma leakage was completed w ithin the first 30 min after challenge. Responses to the mast cell deg ranulator, 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) mo l/site) did not significantly alter the accumulation of In-111-eosinop hil or plasma leakage, whereas these drug doses abolished responses to exogenous PAF (10(-9) mol/site) and arachidonic acid (AA, 3 x 10(-8) mol/site), respectively. The H-1 receptor antagonist chlorpheniramine (2.5 x 10(-8) mol/site) did not reduce antigen-induced In-111-eosinoph il accumulation. Drug combinations were also injected with antigen int o sensitized sites, but were unable to reduce In-111-eosinophil accumu lation. 4 These results indicate that anaphylactic eosinophil accumula tion in this model involves mediators other than histamine, PAF or lip oxygenase products. This is in contrast to plasma leakage in this reac tion, which can be abolished by a combination of antagonists blocking these mediators.