Why is the pathology of falciparum worse than that of vivax malaria?
Here, Ian Clark and Bill Cowden summarize new evidence suggesting that nitric oxide (NO) generated by inducible NO synthase (iNOS) provides a functional link between the previously competing approaches to malarial disease pathogenesis: ischaemic hypoxia and NO. When combined with the newly recognized roles of iNOS in renal and pulmonary function and glucose metabolism, synergy between inflammatory cytokines and hypoxia in iNOS induction provides a framework to help explain, at a molecular level, the differences in the pathology seen in falciparum and vivax malaria. Thus sequestration, through localized hypoxia, might contribute to pathology by enhancing cytokine-induced iNOS. Generalized hypoxia might have the same effect.
Clark
I A
IA
Division of Biochemistry and Molecular Biology, School of Life Sciences, John Curtin School of Medical Research, Australian National University, Canberra, ACT 0200, Australia. ian.clark@anu.edu.au
Cowden
W B
WB
D000818:Animals; D016207:Cytokines / Q000276:immunology; D006019:Glycolysis; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology; D016779:Malaria, Cerebral / Q000209:etiology / Q000503:physiopathology; D016778:Malaria, Falciparum / Q000150:complications / Q000201:enzymology / Q000503:physiopathology*; D016780:Malaria, Vivax / Q000150:complications / Q000276:immunology / Q000503:physiopathology*; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000276:immunology; D019001:Nitric Oxide Synthase / Q000276:immunology; D052247:Nitric Oxide Synthase Type II; D010963:Plasmodium falciparum / Q000472:pathogenicity*; D010966:Plasmodium vivax / Q000472:pathogenicity*; D011654:Pulmonary Edema / Q000469:parasitology / Q000503:physiopathology; D051437:Renal Insufficiency / Q000469:parasitology / Q000503:physiopathology; D014774:Virulence
D016207:Cytokines; D009569:Nitric Oxide; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II