INHIBITION OF THE LIBERATION OF ARACHIDONIC-ACID BY CADMIUM IONS IN RABBIT ALVEOLAR MACROPHAGES

The effects of CdCl2 on the liberation of arachidonic acid (20:4) from membrane phospholipids of A23187-stimulated rabbit alveolar macrophages and on the activity of phospholipase A2 (PLA2) in a cytosolic fraction were studied. Alveolar macrophages were prelabeled with [H-3]arachidonic acid (20:4) and then treated with A23187. This treatment resulted in a remarkable increase in the liberation of [H-3]20:4 from their phospholipids. Exposure of cells to Cd2+ inhibited the liberation of [H-3]20:4 in a dose-dependent manner. Liberation of [H-3]20:4 from cell lipids was calcium dependent and the inhibitory effect of Cd2+ competed with the stimulatory effect of Ca2+. When Ca2+ was removed from the incubation medium, Cd2+ did not influence the liberation of [H-3]20:4. Entry of Ca-45(2+) into cells was enhanced by treatment of A23187. However, Cd2+ did not influence the cellular uptake of Ca-45(2+). Treatment with A23187 markedly enhanced entry of Cd-109(2+) into cells. The effect of Cd2+ on the activity of phospholipase A2 was determined with 1-palmitoyl-2-[C-14]arachidonoyl-sn-glycero-3-phosphocholine as substrate. Calcium-dependent activation of PLA2 was observed and Cd2+ inhibited activation in a dose-dependent manner. These results suggest that exposure of alveolar macrophages to Cd2+ causes a reduction in the rate of liberation of 20:4 from cell lipids, as a possible result of the inhibition of PLA2 activity by Cd2+.