Aggregation of human polymorphonuclear leukocytes by endothelin: role of platelet-activating factor

Author(s): Guerra, M., Gonzalez, E., Lopez-Farre, A., Riesco-Aaramelo, C., Escanero, J., Egido, J.

Journal/Book: European Journal of Pharmacology. 1992; 224(2-3): 167-172.

Abstract: The mechanisms by which endothelin-1 (ET-1) acts on polymorphonuclear leukocytes (PMN) are insufficiently known. In this study, we assessed the hypotheses that ET-1 is a PMN-aggregating agent, and that platelet-activating factor (PAF) is the principal mediator of ET-1-induced PMN aggregation. ET-1 induced dose-related PMN aggregation, which started 1 min after ET-1 exposure. Two different specific PAF receptor antagonists blocked the effect of ET-1 on PMN aggregation. In addition, ET-1 induced a significant increase in the production of PAF by PMN after 2 to 5 min of ET-1 incubation. ET-1 induced PAF release from PMN rather than accumulation. This PAF production was dependent on intra- and extracellular Ca2+. In this regard, the PAF receptor antagonists significantly blunted the ET-1-induced peak in cytosolic free Ca2+ ([Ca2+]i). Our results, therefore, indicate that ET-1 is effective in causing aggregation of human PMN and that its action appears to be mediated by PAF production via a Ca(2+)-dependent mechanism.

Keyword(s): Azepines-pharmacology

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