Role of arachidonic acid in leukotriene B-4-induced guinea-pig eosinophil homotypic aggregation

The activation of eosinophils with the lipid mediator, leukotriene B-4, ind uces their homotypic aggregation. Upon activation with leukotriene B-4, eos inophils release a significant amount of arachidonic acid, a process depend ent on the activation of phospholipase A(2). Here, we have evaluated whethe r arachidonic acid could induce aggregation of eosinophils and whether the release of arachidonic acid mediated the aggregation induced by leukotriene B-4. The exogenous administration of arachidonic acid induced a concentrat ion-dependent eosinophil homotypic aggregation. Pretreatment of eosinophils with a 5-lipoxygenase inhibitor or a leukotriene B-4 receptor antagonist a brogated arachidonic-acid-induced aggregation. Arachidonic acid induced a s ignificant increase in leukotriene B-4 levels and desensitised leukotriene B-4-induced aggregation in a dose-dependent manner. Moreover, this desensit isation was effectively reversed by a 5-lipoxygenase inhibitor. However, ar achidonic acid failed to induce a rise in intracellular Ca2+ in eosinophils and failed to desensitise these cells to rises in intracellular Ca2+ induc ed by leukotriene B-4. Pretreatment of eosinophils with the phospholipase A (2) inhibitor, mepacrine, inhibited the aggregation responses induced by 1 nM leukotriene B-4 by approximately 50% but had no significant effect on th e other concentrations of leukotriene B-4 tested (0.1 to 100 nM). In conclu sion, arachidonic acid stimulates eosinophil aggregation indirectly via the release of leukotriene B-4. Although a significant amount of arachidonic a cid is released in response to activation of eosinophils with leukotriene B -4, the arachidonic acid released does appear to play a major role in media ting leukotriene B-4-induced eosinophil aggregation. (C) 1999 Elsevier Scie nce B.V. All rights reserved.