Presence of Ca²⁺ is obligatory for the cytotoxic activity of dengue virus-induced cytotoxic factor

Abstract

The present study was undertaken to investigate the role of calcium ions (Ca²⁺) in the cytotoxic activity of the cytotoxic factor (CF) produced by T lymphocytes of the dengue type 2 virus (DV)-infected mouse spleen. It was observed that CF prepared in Ca²⁺-free medium had no cytotoxic activity on normal mouse spleen cells suspended in Ca²⁺-free medium but had activity on cells suspended in medium having Ca²⁺. The cytotoxic activity of CF was restored by substitution with calcium chloride, the optimal dose being 10^-7M. CF induced influx of Ca²⁺ as measured by uptake of radiolabelled calcium chloride (⁴⁵Ca), in the susceptible target cells, macrophages (Mφ) and T lymphocytes, but had no effect on CF-resistant B lymphocytes. Calcium channel blocking drugs, like verapamil, nifedipine and diltiazem, inhibited the cytotoxic activity of CF and also the CF-induced influx of ⁴⁵Ca in MφO and T cells. Thus, presence of Ca²⁺ is obligatory for the cytotoxic activity of CF and the cell death is associated with increased intracellular Ca²⁺.