Role of arachidonic acid in leukotriene B4-induced guinea-pig eosinophil homotypic aggregation

Mauro M. Teixeira, Mark A. Lindsay, Mark A. Giembycz, Paul G. Hellewell

Research output: Contribution to journalArticlepeer-review

3 Citations (SciVal)

Abstract

The activation of eosinophils with the lipid mediator, leukotriene B4, induces their homotypic aggregation. Upon activation with leukotriene B4, eosinophils release a significant amount of arachidonic acid, a process dependent on the activation of phospholipase A2. Here, we have evaluated whether arachidonic acid could induce aggregation of eosinophils and whether the release of arachidonic acid mediated the aggregation induced by leukotriene B4. The exogenous administration of arachidonic acid induced a concentration-dependent eosinophil homotypic aggregation. Pretreatment of eosinophils with a 5-lipoxygenase inhibitor or a leukotriene B4 receptor antagonist abrogated arachidonic-acid-induced aggregation. Arachidonic acid induced a significant increase in leukotriene B4 levels and desensitised leukotriene B4-induced aggregation in a dose-dependent manner. Moreover, this desensitisation was effectively reversed by a 5-lipoxygenase inhibitor. However, arachidonic acid failed to induce a rise in intracellular Ca2+ in eosinophils and failed to desensitise these cells to rises in intracellular Ca2+ induced by leukotriene B4. Pretreatment of eosinophils with the phospholipase A2 inhibitor, mepacrine, inhibited the aggregation responses induced by 1 nM leukotriene B4 by approximately 50% but had no significant effect on the other concentrations of leukotriene B4 tested (0.1 to 100 nM). In conclusion, arachidonic acid stimulates eosinophil aggregation indirectly via the release of leukotriene B4. Although a significant amount of arachidonic acid is released in response to activation of eosinophils with leukotriene B4, the arachidonic acid released does appear to play a major role in mediating leukotriene B4-induced eosinophil aggregation. Copyright (C) 1999 Elsevier Science B.V.

Original languageEnglish
Pages (from-to)183-190
Number of pages8
JournalEuropean Journal of Pharmacology
Volume384
Issue number2-3
DOIs
Publication statusPublished - 19 Nov 1999

Bibliographical note

Funding Information:
We are grateful to CNPq, the Wellcome Trust and FAPEMIG for financial support. M.M.T. is a recipient of a CNPq Scientific Development grant.

Keywords

  • 5-Lipoxygenase
  • Aggregation
  • Arachidonic acid
  • Eosinophil
  • Leukotriene B
  • Phospholipase A
  • Signal transduction

ASJC Scopus subject areas

  • Pharmacology

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