Lyso(bis)phosphatidic acid: a novel source of arachidonic acid for oxidative metabolism by rabbit alveolar macrophages.

To identify the source of arachidonic acid utilized for eicosanoid production, rabbit alveolar macrophages were challenged with 1.0 microM 12-O-tetradecanoylphorbol-13-acetate (TPA) or 3.8 microM Ca+2 ionophore A23187 for 3 h. Upon stimulation with TPA, a loss of [3H]arachidonic acid from phosphatidylcholine, phosphatidylethanolamine, lyso(bis)phosphatidic acid, and phosphatidylserine/phosphatidylinositol was observed. Although calcium ionophore stimulated the liberation of arachidonate solely from phosphatidyl-ethanolamine and phosphatidylcholine, it proved to be a poor stimulus for macrophage-synthesis of eicosanoids. Our evidence suggests that degradation of phosphatidylinositol and lyso(bis)phosphatidic acid induced by TPA yields a source of arachidonate which is the preferred substrate for oxidative metabolism by the cyclooxygenase and lipoxygenase pathways.