Investigation of the endogenous chemoattractants involved in ¹¹¹In‐eosinophil accumulation in passive cutaneous anaphylactic reactions in the guinea‐pig

Abstract

6LY1 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 "'In-eosinophils and leakage of '25I-human serum albumin ('251-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 fil, 1/50 dilution). After 20-24 h, animals were injected intravenously with '11In-eosinophils and '25I-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 "'In-eosinophils and plasma leakage in guinea-pig skin. Time course experiments over 24 h revealed that the maximal rate of "'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 (10-1 mol/site) or the 5-lipoxygenase inhibitor, PF 5901 (10-7mol/site) did not significantly alter the accumulation of "'In-eosinophils or plasma leakage, whereas these drug doses abolished responses to exogenous PAF (10-1 mol/site) and arachidonic acid (AA, 3 x I0-mol/site), respectively. The H, receptor antagonist chlorpheniramine (2.5 x 10-8 mol/site) did not reduce antigen-induced "'In-eosinophil accumulation. Drug combinations were also injected with antigen into sensitized sites, but were unable to reduce "'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.

The effect of the selectin binding polysaccharide fucoidin on eosinophil recruitment in vivo

“…Each animal received a duplicate of each treatment following a randomized injection plan and 111 In‐labelled eosinophil accumulation was assessed after 2 h. This time point was chosen based on previous experiments showing that the majority of the 111 In‐eosinophil accumulation induced by ZAP, PAF and in a PCA reaction occurs during the first 90 min and is complete by 120 min after i.d. injection (Faccioli et al , 1991; Weg et al , 1994). At this time, a blood sample was obtained by cardiac puncture, the animals were killed by an overdose of sodium pentobarbitone, the dorsal skin was removed, cleaned free of excess blood and the sites punched out with a 17 mm punch.…”

“…Zymosan‐activated plasma (ZAP) was used as a source of guinea‐pig C5a des Arg and was prepared as previously described (Teixeira et al , 1994). Details of the preparation of IgG 1 ‐rich anti‐BGG anti‐sera and doses of BGG for the PCA reaction are described elsewhere (Weg et al , 1994).…”

“…injection of inflammatory mediators (eg. PAF) or in a passive cutaneous anaphylactic (PCA, type I hypersensitivity) reaction, intravenously‐injected radiolabelled eosinophils accumulate rapidly into the injected skin sites (Teixeira et al , 1993; Weg et al , 1994). Using mAbs directed against cell adhesion molecules, our group has previously shown that radiolabelled eosinophil accumulation in this model is dependent on both CD18 and, to a lesser extent, VLA‐4 present on the eosinophil surface (Weg et al , 1993; Teixeira et al , 1994).…”

Effects of dexamethasone and cyclosporin A on the accumulation of eosinophils in acute cutaneous inflammation in the guinea‐pig

“…For example, after the intradermal injection of PAF and leukotriene B4 (LTB4), over 90% of the total accumulating radiolabelled eosinophils are recruited over the first 90 min (Weg, 1993). A similar rapid accumulation of "'In-eosinophils is observed in a passive cutaneous anaphylactic (PCA) reaction (Weg et al, 1994) where the release of a 5-lipoxygenase metabolite is responsible for the influx of cells (Teixeira & Hellewell, 1994). This rapid influx of eosinophils 'Author for correspondence.…”

“…In guinea-pig skin, radiolabelled eosinophils rapidly accumulate in response to locally-injected mediators or in local allergic reactions (Faccioli et al, 1991;Teixeira et al, 1993a;Weg et al, 1994). For example, after the intradermal injection of PAF and leukotriene B4 (LTB4), over 90% of the total accumulating radiolabelled eosinophils are recruited over the first 90 min (Weg, 1993).…”