GM-CSF-INDUCED PRIMING OF HUMAN NEUTROPHILS FOR ENHANCED PHAGOCYTOSISAND 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 macro phages during infection, was investigated for its effects on human neu trophil-mediated killing of asexual blood forms of Plasmodium falcipar um. 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 expr ession of CR3, Fc-gamma RII and Fc gamma RIII receptors. Treatment of neutrophils with a combination of GM-CSF and TNF resulted in a synergi stic increase in phagocytosis and killing of the parasite. The finding s suggest that GM-CSF is likely to form part of the cytokine network r esponsible for regulating the antiparasitic activity of the neutrophil in malaria.