VERAPAMIL INHIBITS ELASTASE RELEASE AND SUPEROXIDE ANION PRODUCTION IN HUMAN NEUTROPHILS

In response to activation of phagocytic cells and during inflammatory disorders, some proteases and very reactive oxygen species are produce d. These proteases and oxidants are involved in many diseases like tis sue injury or atherosclerosis. We have shown in vitro that verapamil, a calcium channel blocker, had antielastase and antioxidant properties . This drug inhibited the release of elastase by neutrophils in a dose -dependent manner when these cells were stimulated by phorbol-myristat e-acetate (PMA), by N-formyl-methionyl-leucylphenylalanine (fMLP) and by the calcium ionophore A23187 (Ca.I). In addition, verapamil inhibit ed superoxide anion when human neutrophils were stimulated by PMA, fML P, dioctanoylglycerol (DiC8), Ca.I or by opsonised zymosan (OZ). Verap amil did not act by scavenging elastase or oxidants as demonstrated in cell-free models which showed no direct antielastase or antioxidant e ffect involved by verapamil. Superoxide anion and elastase inhibition by verapamil has been considered to the mobilization of cytosolic calc ium and inhibition of protein kinase C. The results suggest that verap amil might contribute help the development and progression of atheroma where oxidants and elastase are involved.