Regulatory interactions between iron and nitric oxide metabolism for immune defense against Plasmodium falciparum infection.

Abstract

Iron chelation therapy of Plasmodium falciparum infection alleviates the clinical course of cerebral malaria in children. This study assessed the underlying mechanisms of this therapy. Cytokine stimulation of human (intestinal cell line DLD-1) or murine cells (murine macrophage cell line RAW 264.7) resulted in increased nitric oxide (NO) formation and decreased survival of plasmodia within cocultured human erythrocytes. The addition of desferrioxamine (DFO) before cytokine treatment increased both NO formation and parasite killing but had no effect in the presence of the inhibitor of NO formation, L-N6-(1-iminoethyl)-lysine. Moreover, peroxynitrite, which is formed after chemical reaction of NO with superoxide, appears to be the principal effector molecule for macrophage-mediated cytotoxicity toward P. falciparum, and interferon-gamma is a major regulatory cytokine for this process. The effect of DFO on the clearance of plasmodia appears to be due to enhanced generation of NO, rather than to limitation of iron availability to the parasite.

• Authors: G Fritsche, C Larcher, H Schennach, G Weiss
• Journal: The Journal of infectious diseases (J Infect Dis) Vol. 183 Issue 9 Pg. 1388-94 (May 01 2001) ISSN: 0022-1899 [Print] United States
• PMID: 11294671 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Iron Chelating Agents
• Lipopolysaccharides
• RNA, Messenger
• Nitric Oxide
• Interferon-gamma
• Iron
• Superoxide Dismutase
• Deferoxamine

Topics

• Animals
• Cells, Cultured
• Coculture Techniques
• Deferoxamine (therapeutic use)
• Erythrocytes (immunology, parasitology)
• Humans
• Interferon-gamma (immunology)
• Iron (metabolism)
• Iron Chelating Agents (therapeutic use)
• Lipopolysaccharides (immunology)
• Macrophages (immunology, parasitology)
• Malaria, Falciparum (drug therapy, immunology)
• Mice
• Nitric Oxide (biosynthesis, toxicity)
• Plasmodium falciparum (drug effects, immunology, metabolism)
• RNA, Messenger (analysis)
• Superoxide Dismutase (metabolism)
• Tumor Cells, Cultured