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To investigate the effect of the heme moiety of malaria pigment, hemozoin, on phagocyte functions, mouse macrophages were fed with insoluble beta-hematin, the synthetic heme-polymer chemically identical to the native pigment, or the soluble monomer, hematin. Production of inflammatory cytokines, interleukin 1 (IL1), tumor necrosis factor alpha (TNF alpha), and nitric oxide (NO) was assayed in the supernatants after stimulation with lipopolysaccharide. The results indicate that both beta-hematin and hematin induce a dose-dependent inhibition of macrophage production of TNF alpha and NO, but not of IL1. One-hour pretreatment with soluble hematin inhibited production of cytotoxic mediators by more than 50% compared to controls, while 6-hr exposure was necessary for insoluble beta-hematin to induce the same level of inhibition. However, the same treatment did not modify the production of TNF alpha and NO by mouse microglia cell lines. The inhibition was partially counterbalanced by adding sulphydryl group donors such as 2-mercaptoethanol, glutathione, or N-acetyl-cysteine during the preincubation time. The results of the present study confirm the inhibitory role of malaria pigment and show that such effect is due to the heme moiety and may be selective for the production of cytotoxic mediators by specific phagocytes. The implications of these findings in the control of malaria infection and disease and in the pathogenesis of severe malaria are discussed.

Original publication

DOI

10.1006/expr.1995.1143

Type

Journal article

Journal

Experimental parasitology

Publication Date

12/1995

Volume

81

Pages

501 - 511

Addresses

Istituto di Microbiologia Medica, Universitá di Milano, Italy.

Keywords

Microglia, Macrophages, Peritoneal, Animals, Mice, Malaria, Nitric Oxide, Sulfhydryl Compounds, Heme, Lipopolysaccharides, Tumor Necrosis Factor-alpha, Hemeproteins, Dose-Response Relationship, Drug, Female