A. Rebollo et al., APOPTOSIS INDUCED BY IL-2 WITHDRAWAL IS ASSOCIATED WITH AN INTRACELLULAR ACIDIFICATION, Experimental cell research, 218(2), 1995, pp. 581-585
It is known that phorbol esters can protect IL-2-dependent lymphocytes
against apoptosis induced by IL-2 withdrawal. However, the mechanism
of this effect remains unclear. In this article we show that apoptosis
induced by IL-2 withdrawal in the CTLL-2 cell line correlates with a
decrease in intracellular pH (pH(i)). Supplementing the incubation med
ium with phorbol esters during IL-2 deprivation protects CTLL-2 cells
against both apoptosis and intracellular acidification. Interestingly,
IL-4 also supports short-term cell survival and maintenance of normal
pH(i). The protein kinase inhibitor staurosporine prevents the protec
tive effects of IL-2, PMA, and IL-4 on apoptosis and intracellular aci
dification. In contrast, inhibition of the Na+/H+ antiporter by 5-N-et
hyl-N-isopropyl amiloride reverts the protective effects of PMA and IL
-4, but only weakly affects IL-8-mediated suppression of apoptosis. Ta
ken together, these results indicate that intracellular acidification
may be an important event during apoptosis induced by IL-2 deprivation
in the CTLL-2 cell line. Moreover, they suggest a key role for protei
n kinase C activation both in the maintenance of pH(i) and in the supp
ression of apoptosis, through mechanisms which rely on the activation
of the Na+/H+ antiporter to a different extent, depending on the rescu
ing factor employed. (C) 1995 Academic Press, Inc.