HUMAN TRACHEAL EPITHELIAL-CELLS SELECTIVELY INCORPORATE 15-HYDROXYEICOSATETRAENOIC ACID INTO PHOSPHATIDYLINOSITOL

15-hydroxyeicosatetraenoic acid (15-HETE) is the major lipoxygenase me tabolite of arachidonic acid produced by human airway epithelial cells . Because HETEs have been shown to be rapidly metabolized and/or incor porated into cellular lipids in other cell types, we investigated the uptake, metabolism, and intracellular distribution of exogenous 15-HET E by primary monolayer cultures of human tracheal epithelial (HTE) cel ls. At concentrations of 0.1 muM, [H-3]15-HETE was rapidly incorporate d by HTE cells and also metabolized primarily by beta-oxidation to sev eral more polar products that were released extracellularly. The major ity of cell-associated [H-3]15-HETE radiolabel was distributed into ph ospholipids, with phosphatidylinositol (PI) accounting for approximate ly 75 % of phospholipid radiolabel. Exogenous 5- and 12-HETE were also metabolized by HTE cells but were less extensively incorporated into phospholipids and were distributed primarily into phosphatidylcholine and phosphatidylethanolamine. Phospholipase A2 hydrolysis indicated se lective esterification of unmodified 15-HETE to the sn-2 position of p hospholipids. 15-HETE incorporation into total phospholipids and into PI was saturable (half maximal incorporation at 0.82 and 0.68 muM, res pectively), while incorporation into neutral lipids continued to incre ase at concentrations of 15-HETE up to 5 muM. The incorporation of 15- HETE into PI was metabolically stable, with an intracellular half-life of 12 h, and was not subject to mobilization in response to 5 muM cal cium ionophore A23187. HTE cells can incorporate and metabolize HETEs that the cells themselves produce as well as those that might be relea sed by inflammatory cells recruited into the airway. The selective and stable incorporation of 15-HETE into PI, a phospholipid intimately in volved in intracellular signal transduction, suggests a potential mech anism by which 15-HETE might participate in the regulation of various epithelial cell functions.