ADHESION MECHANISMS INVOLVED IN C5A-INDUCED EOSINOPHIL HOMOTYPIC AGGREGATION

During the process of migration into tissues, leukocytes interact prim arily with vascular endothelial cells but they have also been shown to interact with each other, In this study we investigated the adhesion mechanisms involved in guinea pig eosinophil homotypic aggregation as assessed by changes in light transmission, The anti-CD18 monoclonal an tibody (mAb) 6.5E, at concentrations in excess of those previously sho wn to abrogate CD18-dependent eosinophil adherence to serum-coated pla stic, inhibited C5a-induced eosinophil aggregation to a maximum of 49- 68%. In contrast, the anti-intercellular adhesion molecule-1 (ICAM-1) mAb RR1/1, which binds to guinea pig eosinophils and has been shown to block guinea pig ICAM-1 function, had no effect on C5a-induced respon ses, Similarly, two functionally active anti-very late antigen-LE (VLA -P) mAbs had no effect on eosinophil aggregation and did not affect th e CD18-independent component of the aggregation response, The role of L-selectin in eosinophil aggregation was investigated by using heparin , the selectin-binding polysaccharide fucoidin, and the anti-L-selecti n mAb MEL-14. Heparin concentration-dependently inhibited C5a- and pla telet- activating factor- (PAF) induced aggregation but C5a-induced re sponses were inhibited more potently, Fucoidin, but not the carbohydra te dermatan sulphate, effectively inhibited C5a-induced eosinophil agg regation, PMA- and PAF-induced responses were also inhibited by fucoid in, Moreover, fucoidin and 6.5E were additive in their ability to inhi bit C5a-induced aggregation, Similarly, MEL-14 effectively inhibited C 5a-induced eosinophil aggregation, In conclusion, we have demonstrated that guinea pig eosinophil homotypic aggregation is meetly dependent on CD11/CD18 and L-selectin present on the eosinophil surface, In addi tion, VLA-4 plays no role in mediating this aggregation response.