Metabolism of leukotrienes by adult and fetal human lungs.

The metabolism of leukotriene (LT) A4, B4, C4, D4, and E4 was studied using both bioassay and reversed phase high performance liquid chromatography (RP-HPLC) methods. The incubation of 20,000 g supernatants of homogenates of human adult lung with LTA4 and LTC4 for various periods of time produced substances of higher biologic activity than the controls (without incubation) when measured on strips of guinea pig lung parenchyma and ileum. RP-HPLC analyses of the incubation media revealed the formation of LTB4, LTC4, LTD4, and LTE4 from LTA4 and the formation of LTD4 and LTE4 from LTC4. LTD4 was converted to LTE4 whereas LTB4 and LTE4 were not catabolized to an appreciable extent during a 2-h incubation period. Supernatants (20,000 g) of human fetal lung homogenates also contain the enzymatic activities to transform LTC4 into LTD4 and LTE4; however, LTA4 was mainly converted to LTB4 and to products of the nonenzymatic hydrolysis of LTA4 such as the delta 6-trans-LTB4, delta 6 -trans-12-epi-LTB4 and the 5,6-dihyroxyeicosatetraenoic acids; much smaller quantities of the peptidoleukotrienes were formed than in adult lung homogenates.