Biphasic effect of cadmium ions on the secretion of leukotriene B4 in rabbit alveolar macrophages

Abstract

 One major role of alveolar macrophages is the production of eicosanoids, which modulate immune and inflammatory processes in the lung. In this study, the effects were investigated of cadmium ions on the secretion of leukotriene (LT)B₄ and prostaglandin (PG)E₂, predominant products of lipoxygenase and cyclooxygenase, respectively. Cd²⁺ had an inhibitory effect on the secretion of LTB₄ and PGE₂ in response to A23187 stimulation at concentrations >3× 10^-5 M. This effect can be explained by the inhibition of arachidonic acid (20 : 4) liberation from membrane phospholipids by Cd²⁺, because Cd²⁺ inhibits both [³H]arachidonic acid (20 : 4) liberation from [³H]20 : 4-prelabeled macrophages and the cytosolic phospholipase A₂ activity. At concentrations <3×10^-5 M, Cd²⁺ had no effect on PGE₂ secretion but showed an augmentation of LTB₄ secretion. In vitro study using macrophage lysate showed enhanced LTB₄ synthesis from arachidonic acid by Cd²⁺, which could be responsible for the augmentation of LTB₄ secretion in cells. These results indicate that Cd²⁺ may increase inflammation by increasing LTB₄ production in lung.