Mercuric chloride induces the production of leukotriene B4 by rabbit alveolar macrophages.

Abstract

The effects of HgCl2 on the production of leukotriene B4 (LTB4) by rabbit alveolar macrophages were investigated. Alveolar macrophages synthesized only a small amount of LTB4 when incubated in Hanks' balanced salt solution (HBSS) in the absence of stimuli or chemical reagents (0.2 +/- 0.1 ng/10(6) cells). The amount of LTB4 synthesized was greatly enhanced when macrophages were incubated with 5 x 10(-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 treatment of [3H]20:4-labeled cells with HgCl2 in a concentration-dependent manner. We confirmed that [3H]20:4 was mainly liberated from the alkenyl 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 [3H]20:4-labeled lysoEGP. When a microsomal fraction prepared from macrophages was added to the same mixture, [3H]20:4 was liberated from [3H]20:4-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 of LTB4 by alveolar macrophages were elevated.