CD14-dependent internalization and metabolism of extracellular phosphatidylinositol by monocytes

We report that membrane CD14 (mCD14), a cell surface receptor found principally on leukocytes, can mediate the uptake and metabolism of extracellular phosphatidylinositol (PtdIns), mCD14 facilitates PtdIns internalization, targeting it to intracellular sites where, following stimulation with a calcium ionophore, it can be acted upon by cytosolic phospholipase A(2). The [C-14]arachidonate released from mCD14-acquired [C-14]arachidonyl-PtdIns is either esterified to triacylglycerol and retained in the cell or secreted as free arachidonate or leukotrienes. Although less than 10% of the arachidonate-derived lipids secreted from endogenous cellular stores are Ei-lipoxygenase metabolites, over one-half of the secreted C-14-lipids derived from mCD14-acquired PtdIns are hydroxyeicosatetraenoic acids or leukotriene B-4, mCD14 may allow these highly active blood cells to acquire and use extracellular Pt-dIns as a source of arachidonate for leukotriene synthesis.