Inhibition of some polymorphonuclear leukocyte functions by ethacrynic acid

Ethacrynic acid (10(-4) M) inhibits exocytosis, phagocytosis and superoxide release in rabbit polymorphonuclear leukocytes (PMN's). Dihydroethacrynic acid is a much weaker inhibitor of these PMN functions. Though ethacrynic acid inhibits ATPase activity in the PMN, this occur at much higher concentrations than required for inhibition of exocytosis and superoxide release, thus a causal relationship seems unlikely. The same applies to inhibition of ATP generation by ethacrynic acid: the concentration required to decrease ATP level in PMN's is much higher than required for the inhibitory effect on exocytosis. Inhibition of exocytosis by ethacrynic acid can be prevented by dithiothreitol. It is concluded that vulnerable sulfhydryl groups are involved in the inhibition by ethacrynic acid.