Plasmodium falciparum Malaria: reduction of endothelial cell apoptosis in vitro.
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.
Hemmer
Christoph Josef
CJ
University of Rostock Medical School, Division of Tropical Medicine and Infectious Diseases, Department of Medicine, Ernst-Heydemann-Strasse 6, 18057 Rostock, Germany. Christoph_Hemmer@med.uni-rostock.de.
Lehr
Hans Anton
HA
Westphal
Kathi
K
Unverricht
Marcus
M
Kratzius
Manja
M
Reisinger
Emil Christian
EC
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology; D006801:Humans; D007106:Immune Sera / Q000276:immunology; D016778:Malaria, Falciparum / Q000276:immunology* / Q000401:mortality / Q000469:parasitology / Q000503:physiopathology; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D010963:Plasmodium falciparum / Q000472:pathogenicity*; D011480:Protease Inhibitors / Q000494:pharmacology*; D014471:Umbilical Veins
D000975:Antioxidants; D007106:Immune Sera; D011480:Protease Inhibitors
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