Plasmodium falciparum pigment induces monocytes to release high levels of tumor necrosis factor-alpha and interleukin-1 beta.
We show that high levels of tumor necrosis factor-alpha (TNF-alpha) activity were consistently detected when monocytes were cocultured with Plasmodium falciparum schizont stage-parasitized erythrocytes that subsequently ruptured. Isolated pigment recovered from ruptured schizonts was found to specifically induce monocyte release of high levels of TNF-alpha and interleukin-1 beta (IL-1 beta). Particulate free-culture supernatant that contained various soluble parasite macromolecules induced relatively low levels of TNF-alpha and IL-1 beta. When isolated pigment was treated with protease, the monokine inducing-activity was abolished. Isolated pigment prepared from different natural isolates of P. falciparum stimulated variable levels of monokine production. We propose that in vivo, malaria pigment from parasites sequestered in the host microvasculature is a physiologically relevant moiety that interacts with monocytes and stimulates the release of TNF-alpha and IL-1 beta. These observations suggest that malaria pigment may be a virulence factor in the monokine-mediated induction of organ-specific and systemic pathophysiology in falciparum malaria.
Pichyangkul
S
S
Department of Immunology and Parasitology, U.S. Army Medical Component, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand.
Saengkrai
P
P
Webster
H K
HK
D000818:Animals; D002448:Cell Adhesion; D002499:Centrifugation, Density Gradient; D010450:Endopeptidases / Q000378:metabolism; D004912:Erythrocytes / Q000469:parasitology; D006427:Hemin / Q000494:pharmacology; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism*; D008049:Lipase / Q000378:metabolism; D008863:Microspheres; D009000:Monocytes / Q000187:drug effects / Q000276:immunology*; D010587:Phagocytosis; D010860:Pigments, Biological / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D010963:Plasmodium falciparum / Q000737:chemistry / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D007375:Interleukin-1; D010860:Pigments, Biological; D014409:Tumor Necrosis Factor-alpha; D006427:Hemin; D008049:Lipase; D010450:Endopeptidases