Evidence for two sources of arachidonic acid for oxidative metabolism by mouse peritoneal macrophages.

The products of arachidonic acid oxygenations by resident mouse peritoneal macrophages have been found to depend upon the nature of the stimulus. For example, soluble membrane-mediated inflammatory stimuli such as phorbol myristate acetate and lipopolysaccharide stimulated the formation of prostaglandin E2 via the cyclooxygenase pathway. In contrast, zymosan, a particulate, phagocytozable inflammatory mediator stimulated leukotrienes C4 and B4 synthesis via the lipoxygenase pathway in addition to stimulating prostaglandin E2 synthesis. Thus, the release of leukotrienes is not necessarily linked to the release of prostaglandins in a cell that has the enzymatic capability of producing both mediators. This suggests that the prostaglandin synthetase system can obtain substrate arachidonic acid from a source different from that for leukotriene synthesis.