A23 187 stimulates the metabolism of endogenous as well as exogenous arachidonic acid (AA) and eicosapentaenolc acid (EPA) to their corresponding leukotrienes in human neutrophils. In contrast, conflicting results have been obtained concerning the effect of FMLP on the metabolism of these fatty acids. In the present study we compared the effect of A23187 and FMLP on the release and metabolism of these fatty acids in neutrophils. Stimulation of neutrophils with A23187, but not with FMLP, resulted in detectable levels of AA in the presence or absence of BW755C (a dual inhibitor of cyclooxygenase and lipoxygenase). The absolute amount of nonesterified AA in the extracts of neutrophils exposed to the agonist A23187 in the presence of BW755C was 20% higher than that obtained in the absence of BW755C, indicating that only a small fraction of the released AA was converted to lipoxygenase products. Furthermore, significant quantities of AA and EPA metabolites were detected only after treatment of neutrophils with A231 87, but not with FMLP. Both A23187 and FMLP stimulated the conversion of exogenous EPA to 5-lipoxygenase products, with A23 187 being somewhat more effective. In addition, significant differences were noted on the effect of EPA and DHA on the conversion of AA to its metabolites in A23 187-stimulated neutrophils. Our results provide strong evidence that the amounts of eicosanoid precursors mobilized in response to FMLP are extremely small, if any, and this appears to be the likely explanation for the lack of eicosanoid detection by HPLC in FMLP-stimulated neutrophils.
Key w o n k arachidonic acid, neutrophilf, eicapapencaenOic acid
It is becoming increasingly apparent that arachidonic acid and its metabolites play a predominant role in several inflammatory processes [ 1-31. For example, leukotriene B, (LTB,) is known to stimulate neutrophil chemotaxis and other functions [&7]. Recently, a great deal of interest has arisen concerning the potential dampening effects of Abbreviations used: BW755C, 3-amino-1-(3-trifluoromethylphenyl-2-pyrazoliie) hydrochloride (a dual inhibitor of cyclooxygenase and lipoxygenases); FMLP, fmet-Leu-Phe.