Cytokine-mediated Inactivation of Malarial Gametocytes is Dependent on the Presence of White Blood Cells and Involves Reactive Nitrogen Intermediates

Supernatants of human peripheral blood mononuclear cells (PBMC) incubated for 24 hr in the presence of extracts of freeze-thawed blood stage parasites of Plasmodium vivax or P. falciparum mediate inactivation of gametocytes of either species when incubated in vitro with whole human blood cells. Cultured P. falciparum gametocytes incubated with these malaria extract-stimulated PBMC supernatants in the presence of human blood from which white blood cells (WBC) had been removed were not inactivated. Thus the effects of the PBMC supernatants on gametocyte infectivity were dependent upon the presence of WBC. The suppressive effects mediated in the presence of WBC could be partially reversed in the presence of concentrations of 1 mM or higher of the L-arginine analogue NGL-monomethyl arginine acetate (L-NMMA). Our results indicate that the effects of WBC in inactivating gametocytes are due, at least in part, to a mechanism involving an L-arginine-dependent pathway. Previous studies have shown that the mediators of gametocyte inactivation in the stimulated PBMC supernatants comprised tumour necrosis factor (TNF) acting in conjunction with unidentified, but essential, 'complementary factors'. In the present study we show that these mediators, TNF and complementary factors, affect gametocytes indirectly through their interaction with WBC.