Transcellular Metabolism of Arachidonic Acid in Platelets and Polymorphonuclear Leukocytes Activated by Physiological Agonists: Enhancement of Leukotriene B4Synthesis
Polymorphonuclear leukocytes (PMNL) are known to play a major role in the inflammatory process in part through their ability to produce and respond to chemotactic factors. Leukotriene (LT) B4, a metabolite of arachidonic acid derived from the 5-lipoxygenase pathway, is produced by phagocytes and has potent chemotactic and chemokinetic effects on these cells1. PMNL stimulated with the ionophore A23187 synthesize large amounts of LTB4 2, while receptor-mediated activation of PMNL and monocytes-macrophages by agonists such as the chemotactic peptide N-formyl-Met-Leu-Phe (fMLP), the complement fragment C5a, platelet-activating factor (paf-acether) or by phagocytosis also leads to LTB4 synthesis3–7. However LTB4 synthesis induced by natural agonists is of lower magnitude as it is often not detectable by HPLC procedures8. Evidence has accumulated during the last decade, supporting that platelet/leukocyte interactions occur in several pathophysiological situations9, and in particular that platelets might modulate inflammation. Indeed, activated platelets release arachidonic acid metabolites, pafacether, platelet-derived growth factor (PDGF), platelet factor 4 (PF4), serotonin and adenine nucleotides which could affect PMNL functions such as migration, degranulation, adherence and production of superoxide anion10–13.
KeywordsArachidonic Acid Tiaprofenic Acid Arachidonic Acid Metabolite Glyceryl Ether Human Polymorphonuclear Leukocyte
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