BIPHASIC EFFECT OF CADMIUM IONS ON THE SECRETION OF LEUKOTRIENE B-4 IN RABBIT ALVEOLAR MACROPHAGES

One major role of alveolar macrophages is the production of eicosanoid s, which modulate immune and inflammatory processes in the lung. In th is study, the effects were investigated of cadmium ions on the secreti on of leukotriene (LT)B-4 and prostaglandin (PG)E(2), predominant prod ucts of lipoxygenase and cyclooxygenase, respectively. Cd2+ had an inh ibitory effect on the secretion of LTB(4) and PGE(2) in response to A2 3187 stimulation at concentrations > 3 x 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 [H-3] arac hidonic acid (20:4) liberation from [H-3]20:4-prelabeled macrophages a nd the cytosolic phospholipase A(2) activity. At concentrations < 3 x 10(-5) M, Cd2+ had no effect on PGE(2) secretion but showed an augment ation of LTB(4) secretion. In vitro study using macrophage lysate show ed enhanced LTB(4) synthesis from arachidonic acid by Cd2+, which coul d be responsible for the augmentation of LTB(4) secretion in cells. Th ese results indicate that Cd2+ may increase inflammation by increasing LTB(4) production in lung.