L‐Arginine‐dependent destruction of intrahepatic malaria parasites in response to tumor necrosis factor and/or interleukin 6 stimulation

Abstract

There is growing evidence that cytokines (interleukin [IL] 1, IL 6, interferon-gamma, tumor necrosis factor [TNF]) directly or indirectly interfere with the intrahepatic development of malaria parasites. Recent work in our laboratory clearly showed that TNF can affect the hepatic development of parasites via IL 6 secreted by liver nonparenchymal cells. The possible participation of an L-arginine-dependent effector mechanism has been studied to explain the TNF/IL 6-induced inhibition. We thus investigated if NGmonomethyl-L-arginine and N omega-nitro-L-arginine, two specific inhibitors of inorganic nitrogen oxide synthesis from L-arginine, were able to affect the inhibitory effect of TNF and/or IL 6 in co-cultures. At 0.1 and 0.5 mM both L-arginine analogues reversed the inhibitory effect of these cytokines. An interesting observation is that L-arginine analogues enhance schizont development in the absence of prior cytokine contact. This result indicates an hepatic basal L-arginine-dependent anti-parasitic activity which might explain the existence of self-degenerating hepatic forms as previously reported.

Pattern of Kvβ Subunit Expression in Macrophages Depends upon Proliferation and the Mode of Activation

“…However, the endotoxin is the most powerful NO-stimulating agent (50). High intracellular concentrations of NO would increase the oxidative stress of BMDM, thereby contributing to the pathogenesis of septic shock (51). Thus, an increase in oxidative stress generated by LPS and, to a lesser extent, TNF-␣ could modulate Kv␤ activity, leading to a precise Kv functional role.…”

Identification of frequently recognized dimorphic T-cell epitopes in plasmodium falciparum merozoite surface protein-1 in West and East Africans: lack of correlation of immune recognition and allelic prevalence.

“…11,16,17 IFN-␥ can activate non-lymphocytic effector cells such as monocytes 34,35 to control parasite growth through phagocytosis, 36 generate reactive oxygen intermediates 37 or L-arginine-derived nitric oxide. 38,39 However, IFN-␥ does not control parasite growth by direct elimination of intra-erythrocytic parasites. [40][41][42] In the present study, frequently recognized T-cell epitopes of MSP1 distributed throughout the protein were identified in naturally exposed malaria adults in The Gambia.…”

Non specific resistance against malaria pre-erythrocytic stages: involvement of acute phase proteins

“…Different mechanisms, involving both specific and non-specific components of the host response against infection, contribute to control malaria parasite development in the liver (Mazier et al, 1990;Rénia et al, 1991;Schofield et al, 1988;Schofield et al, 1989;Weiss et al, 1988;Weiss et al, 1990). Experimentally, there is evidence that acute phase proteins synthetized by the hepatocyte in response to cytokine stimulation also protect hepatocyte against sporozoite infection (Mellouk et al, 1987 1991a, 1991bPied et al, 1989Pied et al, , 1990. APPs are plasma proteins whose concentrations vary during an inflammatory reaction.…”