Correlation Between Destruction of Malarial Parasites by Polymorphonuclear Leucocytes and Oxidative Stress

Golenser, Jacob; Kamyl, M.; Tsafack, A; Marva, Esther; Cohen, A.; Kitrossky, Nahum; Chevion, Mordechai

doi:10.3109/10715769209079517

Cited by 31 publications

(22 citation statements)

References 30 publications

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“…Activated neutrophils and their secretory products may generate not only antiparasitic activity (16) but also endothelial damage (55), which can lead to organ failure in severe malaria. We have previously found that in synergism with neutrophils, sera from patients with complicated malaria damage endothelial cells in vitro (23).…”

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confidence: 99%

Plasmodium falciparumMalaria: Reduction of Endothelial Cell Apoptosis In Vitro

Hemmer

Lehr²,

Westphal

et al. 2005

Infect Immun

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Organ failure in Plasmodium falciparum malaria is associated with neutrophil activation and endothelial damage. This study investigates whether neutrophil-induced endothelial damage involves apoptosis and whether it can be prevented by neutralization of neutrophil secretory products. Endothelial cells from human umbilical veins were coincubated with neutrophils from healthy donors and with sera from eight patients with P. falciparum malaria, three patients with P. vivax malaria, and three healthy controls. Endothelial apoptosis was demonstrated by terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) and annexin V staining. The rate of apoptosis of cells was markedly increased after incubation with patient serum compared to that with control serum. Apoptosis was most pronounced after incubation with sera from two patients with fatal cases of P. falciparum malaria, followed by sera of survivors with severe P. falciparum malaria and, finally, by sera of patients with mild P. falciparum and P. vivax malaria. Ascorbic acid, tocopherol, and ulinastatin reduced the apoptosis rate, but gabexate mesilate and pentoxifylline did not. Furthermore, in fatal P. falciparum malaria, apoptotic endothelial cells were identified in renal and pulmonary tissue by TUNEL staining. These findings show that apoptosis caused by neutrophil secretory products plays a major role in endothelial cell damage in malaria. The antioxidants ascorbic acid and tocopherol and the protease inhibitor ulinastatin can reduce malaria-associated endothelial apoptosis in vitro.

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confidence: 99%

Plasmodium falciparumMalaria: Reduction of Endothelial Cell Apoptosis In Vitro

Hemmer

Lehr²,

Westphal

et al. 2005

Infect Immun

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“…Leukocytes from mice (9,25,43,44,62,71) and humans (2,12,23,49,58) infected with malaria show an increased ability to generate ROS. Leukocytes stimulated with malaria parasites in vitro generate ROS, and in some cases this has been linked to damage to the parasites in human (33,40,50) and murine (51) systems. However, ROS do not account for all the antimalarial activity of human leukocytes in such in vitro systems (41,50).…”

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confidence: 99%

Phagocyte-Derived Reactive Oxygen Species Do Not Influence the Progression of Murine Blood-Stage Malaria Infections

et al. 2005

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Phagocyte-derived reactive oxygen species have been implicated in the clearance of malaria infections. We investigated the progression of five different strains of murine malaria in gp91 phox؊/؊ mice, which lack a functional NADPH oxidase and thus the ability to produce phagocyte-derived reactive oxygen species. We found that the absence of functional NADPH oxidase in the gene knockout mice had no effect on the parasitemia or total parasite burden in mice infected with either resolving (Plasmodium yoelii and Plasmodium chabaudi K562) or fatal (Plasmodium berghei ANKA, Plasmodium berghei K173 and Plasmodium vinckei vinckei) strains of malaria. This lack of effect was apparent in both primary and secondary infections with P. yoelii and P. chabaudi. There was also no difference in the presentation of clinical or pathological signs between the gp91 phox؊/؊ or wild-type strains of mice infected with malaria. Progression of P. berghei ANKA and P. berghei K173 infections was unchanged in glutathione peroxidase-1 gene knockout mice compared to their wild-type counterparts. The rates of parasitemia progression in gp91 phox؊/؊ mice and wild-type mice were not significantly different when they were treated with L-N G -methylarginine, an inhibitor of nitric oxide synthase. These results suggest that phagocyte-derived reactive oxygen species are not crucial for the clearance of malaria parasites, at least in murine models.

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“…Radicais oxidantes gerados em hemácias parasitadas também podem causar a elevação dos níveis de metemoglobina. Um estudo in vitro demonstrou haver elevação dos níveis de metemoglobina em hemácias parasitadas pelo Plasmodium falciparum 15 . O fato dos sujeitos desta pesquisa serem indivíduos com malária não interferiu nos resultados relacionados à metemoglobina circulante, pois nenhum destes apresentou malária grave.…”

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