Title: Leukotriene D4-metabolizing activity of human neutrophils.
Abstract:Leukotriene D4-metabolizing activity was studied using human neutrophils. Leukotriene D4 was rapidly converted to leukotriene E4 during incubation with intact neutrophils. The subcellular localization...Leukotriene D4-metabolizing activity was studied using human neutrophils. Leukotriene D4 was rapidly converted to leukotriene E4 during incubation with intact neutrophils. The subcellular localization of leukotriene D4-metabolizing enzyme was examined, and leukotriene D4-metabolizing activity was found to be present in the particulate fraction which consists of cell surface membrane and granules, but not in the nuclear and cytosol fractions. When neutrophils were modified chemically with diazotized sulfanilic acid, a poorly permeant reagent which inactivates cell surface enzymes selectively, the leukotriene D4-metabolizing activity of intact neutrophils was significantly inhibited. When neutrophils were stimulated with phorbol myristate acetate, a secretagogue, leukotriene D4-metabolizing activity was found to be released extracellularly. Among enzyme inhibitors examined, o-phenanthroline, a metal chelator strongly inhibited both the leuko-triene D4-metabolizing activities of intact neutrophils and extracellularly released enzyme. These results would suggest that leukotriene D4-metabolizing metalloenzymes which convert leukotriene D4 to leukotriene E4, are located on the cell surface membrane and in the granules of human neutrophils.Read More