15-hydroxyeicosatetraenoic acid (15-HETE) is the major lipoxygenase metabolite of arachidonic acid produced by human airway epithelial cells. Because HETEs have been shown to be rapidly metabolized and/or incorporated into cellular lipids in other cell types, we investigated the uptake, metabolism, and intracellular distribution of exogenous 15-HETE by primary monolayer cultures of human tracheal epithelial (HTE) cells. At concentrations of 0.1 microM, [3H]15-HETE was rapidly incorporated by HTE cells and also metabolized primarily by beta-oxidation to several more polar products that were released extracellularly. The majority of cell-associated [3H]15-HETE radiolabel was distributed into phospholipids, with phosphatidylinositol (PI) accounting for approximately 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 selective esterification of unmodified 15-HETE to the sn-2 position of phospholipids. 15-HETE incorporation into total phospholipids and into PI was saturable (half maximal incorporation at 0.82 and 0.68 microM, respectively), while incorporation into neutral lipids continued to increase at concentrations of 15-HETE up to 5 microM. 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 microM calcium ionophore A23187. HTE cells can incorporate and metabolize HETEs that the cells themselves produce as well as those that might be released by inflammatory cells recruited into the airway.(ABSTRACT TRUNCATED AT 250 WORDS)