MERCURIC-CHLORIDE INDUCES THE PRODUCTION OF LEUKOTRIENE B-4 BY RABBITALVEOLAR MACROPHAGES

The effects of HgCl2 on the production of leukotriene B-4 (LTB(4)) by rabbit alveolar macrophages were investigated. Alveolar macrophages sy nthesized only a small amount of LTB(4) when incubated in Hanks' balan ced salt solution (HBSS) in the absence of stimuli or chemical reagent s (0.2 +/- 0.1 ng/10(6) cells). The amount of LTB(4) synthesized was g reatly enhanced when macrophages were incubated with 5x10(-6) M HgCl2 (5.3 +/- 0.2 ng/10(6) cells). Increases in levels of free arachidonic acid (20:4), a precursor of eicosanoids, were also observed on treatme nt of [H-3]20:4-labeled cells with HgCl2 in a concentration-dependent manner. We confirmed that [3H]20:4 was mainly liberated from the alken yl subclass of ethanolamine glycerophospholipids (EGP). Degradation of alkenyl-EGP was also observed when HgCl2 and [3H]20:4-labeled lipids were incubated in HBSS, resulting in an increase in the level of [H-3] 20:4-labeled lysoEGP. When a microsomal fraction prepared from macroph ages was added to the same mixture, [3H]20:4 was liberated from [H-3]2 0:4-containing lysoEGP. These results suggest that the alkenyl linkage of EGP was degraded in the presence of HgCl2 with resultant formation of lysoEGP which was subsequently hydrolyzed by lysophospholipase. As a consequence, the level of free 20:4 in and the rate of production o f LTB(4) by alveolar macrophages were elevated.