GM-CSF-induced priming of human neutrophils for enhanced phagocytosis and killing of asexual blood stages of Plasmodium falciparum: synergistic effects of GM-CSF and TNF.
Granulocyte macrophage-colony stimulation factor (GM-CSF), which is a haematopoietic cytokine generated by activated T lymphocytes and macrophages during infection, was investigated for its effects on human neutrophil-mediated killing of asexual blood forms of Plasmodium falciparum. Pretreatment of neutrophils with human recombinant-GM-CSF markedly increased the parasite killing (measured by a radiometric assay), in the presence of normal serum (containing complement), immune serum (IS), purified IgG (from IS) or heat inactivated IS. GM-CSF pretreatment also enhanced phagocytosis of the parasite by neutrophils and the expression of CR3, Fc gamma RII and Fc gamma RIII receptors. Treatment of neutrophils with a combination of GM-CSF and TNF resulted in a synergistic increase in phagocytosis and killing of the parasite. The findings suggest that GM-CSF is likely to form part of the cytokine network responsible for regulating the antiparasitic activity of the neutrophil in malaria.
Kumaratilake
L M
LM
Department of Immunology, Women's and Children's Hospital, Adelaide, Australia.
Ferrante
A
A
Jaeger
T
T
Rzepczyk
C
C
D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology; D000962:Antimalarials / Q000494:pharmacology*; D004357:Drug Synergism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D016177:Macrophage-1 Antigen / Q000096:biosynthesis; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology*; D010587:Phagocytosis; D010963:Plasmodium falciparum / Q000254:growth & development / Q000276:immunology*; D017452:Receptors, IgG / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D000913:Antibodies, Protozoan; D000962:Antimalarials; D016177:Macrophage-1 Antigen; D017452:Receptors, IgG; D014409:Tumor Necrosis Factor-alpha; D016178:Granulocyte-Macrophage Colony-Stimulating Factor