Killing of human malaria parasites by macrophage secretory products

Abstract

The susceptibility of the human malaria parasite, Plasmodium falciparum, to killing in vitro by macrophage secretory products was investigated. The effect of 02 radicals and tumor necrosis factor on parasite viability was assessed both morphologically and by following the uptake of [3H]hypoxanthine. H202 produced by the interaction of glucose and glucose oxidase was found to reduce viability; this effect was reversed by the addition of exogenous catalase. Further studies indicated that the catalase level within the erythrocyte was not altered upon parasite invasion. 02 radicals produced during the xanthine-xanthine oxidase interaction also killed P. falciparum. The addition of various 02 radical scavengers (including catalase) did not reverse this effect; therefore, it was not possible to determine which of the 02 radicals were involved in the killing process. Samples from three different sources containing tumor necrosis factor, a nonspecific soluble mediator derived from Mycobacterium bovis BCG-activated macrophages treated with endotoxin, also killed the parasite. There was no evidence that tumor necrosis factor or the products of the xanthine-xanthine oxidase interaction caused damage to the erythrocyte membrane that could be implicated as an important aspect of the killing process. These findings all strongly suggest that such macrophage products play an important role in immunity to malaria. * Corresponding author. was assessed both morphologically and by measuring the uptake of [3H]hypoxanthine over a 24-h period after treatment. MATERIALS AND METHODS Parasites. P. falciparum (Wellcome/Liverpool strain) was maintained by routine cultivation procedures (26), using RPMI 1640 medium supplemented with 15% ARh+ human serum and N-tris(hydroxymethyl)methyl-2-aminoethane sul

Generation of Reactive Oxygen Radicals by Human Phagocytic Cells Activated by Plasmodium falciparum

“…17, 25]. The parasite destruction has been shown to be mediated through several different products of these cells, such as reactive oxygen radicals [24,34], Oxygen-independent components (18, 23). and tumuor necrosis factor [12,30].…”

Malaria parasite‐specific Th1‐like T cells simultaneously reduce parasitemia and promote disease

“…Furthermore, interferon (IFN)-g and tumour necrosis factor (TNF)-a are known to be able to inhibit parasite growth in vivo (Taverne et al 1987, Shear et al 1989, Stevenson & Ghadirian 1989), suggesting that parasite-activated T cells might work via a cytokine cascade, probably in the spleen (Kumar et al 1989, Favila-Castillo et al 1996. Although the final effector molecules that mediate parasite death are not known, reactive nitrogen intermediates (Rockett et al 1991, Taylor-Robinson et al 1993, Jacobs et al 1995, and oxygen radicals (Clark & Hunt 1983, Wozencraft et al 1984 have been implicated.…”

Changes in the superoxide anion generating capacity and respiratory burst enzymes of peripheral blood monocytes of monkeys during acute Plasmodium knowlesi infection

“…Oxygen free radicals generated in vitro by enzyme substrate systems of xanthine-xanthine oxidase and glucose-glucose oxidase (Wozencraft et al 1984) or in vivo by injecting alloxan (Clark & Hunt 1983) or phenylhydrazine (Rigdon, Micks & Brestia 1950), have been shown to kill human, murine and simian malarial parasites respectively. Apart from these, oxygen free radicals are also known to be generated by phagocytic cells when encountered with particulate or soluble stimuli (Badwey & Karnovsky 1980).…”