Metabolism of leukotriene A4 by an enzyme in blood plasma: a possible leukotactic mechanism.

Cell-free mammalian plasma transformed leukotriene A4 into leukotriene B4. This conversion originated from a soluble enzymatic activity. Heating at 56 degrees C or digestion of plasma with a proteolytic enzyme eliminated formation of leukotriene B4 but not other diastereomeric dihydroxyicosatetraenoic acids formed by nonenzymatic hydrolysis of leukotriene A4. Plasma from several mammals, including guinea pigs, pigs, cows, sheep, rabbits, rats, dogs, and humans, exhibited a qualitatively similar activity. Maximal production of leukotriene B4 occurred in guinea pig plasma near a pH of 7.6; metabolic capacity approached saturation at a substrate concentration of 10 microM. Leukotriene A4 anion was transformed but not its methyl ester. The results suggest that conversion of leukotriene A4 by an enzyme in blood plasma of mammals may provide local gradients of the chemotactic substance leukotriene B4. High interfacial concentrations of leukotriene B4 between the vascular endothelium and leukocytes could facilitate their diapedesis and accumulation at inflammatory sites.