Arachidonate metabolism by human polymorphonuclear leukocytes stimulated by N-formyl-Met-Leu-Phe or complement component C5a is independent of phospholipase activation.

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Abstract
Release of arachidonic acid by the membrane phospholipase and metabolism by the 5-lipoxygenase pathway was examined in human polymorphonuclear leukocytes (PMN). The 5-lipoxygenase pathway is activated when PMN are given arachidonic acid in ethanol and there is extensive metabolism to 5-hydroxyeicosatetraenoic acid (5-HETE) and leukotriene B4 (LTB4). This activation event was altered by the ethanol because resting PMN given arachidonic acid with bovine serum albumin fail to metabolize arachidonic acid. Cells activated by the inflammatory agents N-formyl-Met-Leu-Phe (fMLF) or complement component C5a recruit the 5-lipoxygenase to metabolize exogenous arachidonic acid to 5-HETE and LTB4. When PMN were incubated with arachidonic acid-bovine serum albumin and challenged with fMLF or C5a (des-Arg-C5a) they produced 49-75 pmol of LTB4 and 310-440 pmol of 5-HETE per 107 cells. PMN stimulated by fMLF or C5a (des-Arg-C5a) do not induce membrane phospholipases to mobilize endogenous arachidonic acid and neither 5-HETE nor LTB4 is formed. PMN stimulation by the ionophore A23187 [calcimycin] activates both the membrane phospholipase and the 5-lipoxygenase to produce 5-HETE and LTB4 from endogenous arachidonic acid. The lipoxygenase pathway is apparently inoperative in resting PMN but can be recruited to chemotactic factors to act on arachidonate from extracellular sources. It was previously believed that the results refute the concept that formation of 5-HETE and LTB4 by the PMN depends solely on phospholipase to mobilize endogenous arachidonic acid and indicate that the role of phospholipase activation in PMN may be overestimated. Subsequent involvement of lipoxygenase products in mediating stimulation of PMN by inflammatory factors (e.g., as in aggregation and chemotaxis) remains in question unless an exogenous source of arachidonate can be identified.

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