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Redox‐Dependent Apoptosis in Human Endothelial Cells after Adhesion of Plasmodium falciparum ‐Infected Erythrocytes
Author(s) -
PINO PACO,
VOULDOUKIS IOANNIS,
DUGAS NATHALIE,
HASSANILOPPION GERALDINE,
DUGAS BERNARD,
MAZIER DOMINIQUE
Publication year - 2003
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1299.109
Subject(s) - apoptosis , microbiology and biotechnology , oxidative stress , biology , inflammation , plasmodium falciparum , chemistry , immunology , biochemistry , malaria
A bstract : During Plasmodium falciparum infection leading to cerebral malaria, mechanisms such as cytokine generation and cytoadherence of parasitized red blood cells (PRBC) to post‐capillary venules are clearly involved. We demonstrated that PRBC adhesion to human lung endothelial cells (HLEC) upregulated TNF‐α superfamily genes and genes related to apoptosis and inflammation. Apoptosis was confirmed by standard techniques (annexin‐V binding, genomic DNA fragmentation, and caspases activation). This apoptotic process involved the cytoplasmic pathway from a death receptor (DR‐6, Fas, TNF‐R1) through caspase 8, and the mitochondrial pathway though Bad and caspase 9 activation. Oxidative stress has been implicated in apoptosis induction in various pathological models. Superoxide anion (O 2 • ‐ ) is a key molecule in the oxidative stress pathway which can form peroxynitrites (ONOO ‐ ) in association with nitric oxide (NO•). Even though the role of NO• in malaria physiopathology is still a matter of controversy, we demonstrated that PRBC‐induced apoptosis in endothelial cells is mediated through an oxidative stress pathway. The inhibition of NO• synthesis protected the endothelial cells suggesting a deleterious role for NO•. In addition, the superoxide dismutase mimetic, MnTBAP, also protected the HLEC against PRBC‐induced apoptosis, revealing the role of O 2 • ‐ and ONOO ‐ .