N. Kudo et K. Waku, MERCURIC-CHLORIDE INDUCES THE PRODUCTION OF LEUKOTRIENE B-4 BY RABBITALVEOLAR MACROPHAGES, Archives of toxicology, 68(3), 1994, pp. 179-186
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.