Metabolism of Leukotrienes by Adult and Fetal Human Lungs

Abstract

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 bomogenates 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-b incubation period. Supernatants (20,000 g) of buman fetal lung homogenates also contain the enzymatic activities to transform LTC₄ into LTD₄ and LTE₄; bowever, LTA₄, was mainly converted to LTB₄ and to products of the nonenzymatic hydrolysis of LTAs, such as the δ⁶-trans-LTB₄, δ⁶-trans-12-epi-LTBδ⁶ and the 5,6-dihyroxy-eicosatetraenoic acids; much smaller quantities of the peptidoleukotrienes were formed than in adult lung homogenates.