THE HEME MOIETY OF MALARIA PIGMENT (BETA-HEMATIN) MEDIATES THE INHIBITION OF NITRIC-OXIDE AND TUMOR-NECROSIS-FACTOR-ALPHA PRODUCTION BY LIPOPOLYSACCHARIDE-STIMULATED MACROPHAGES
D. Taramelli et al., THE HEME MOIETY OF MALARIA PIGMENT (BETA-HEMATIN) MEDIATES THE INHIBITION OF NITRIC-OXIDE AND TUMOR-NECROSIS-FACTOR-ALPHA PRODUCTION BY LIPOPOLYSACCHARIDE-STIMULATED MACROPHAGES, Experimental parasitology, 81(4), 1995, pp. 501-511
To investigate the effect of the heme moiety of malaria pigment, hemoz
oin, 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 inflamm
atory cytokines, interleukin 1 (IL1), tumor necrosis factor alpha (TNF
alpha), and nitric oxide (NO) was assayed in the supernatants after s
timulation with lipopolysaccharide. The results indicate that both bet
a-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 m
ore than 50% compared to controls, while 6-hr exposure was necessary f
or insoluble beta-hematin to induce the same level of inhibition. Howe
ver, the same treatment did not modify the production of TNF alpha and
NO by mouse microglia cell lines. The inhibition was partially counte
rbalanced 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 pi
gment and show that such effect is due to the heme moiety and may be s
elective for the production of cytotoxic mediators by specific phagocy
tes. The implications of these findings in the control of malaria infe
ction and disease and in the pathogenesis of severe malaria are discus
sed. (C) 1995 Academic Press. Inc.