Plasmodium falciparum: Characterization of toxin-associated proteins and identification of a hemoglobin containing parasite cytokine stimulator

Previous studies have indicated that inositol monophosphate (IMP) is a component of the malaria parasite toxin that induces cytokines such as tumour necrosis factor (TNF). To further characterize the toxin we have labeled Plasmodium falciparum in vitro cultures with [C-14]inositol or [S-35]-methionine and immunoprecipitated the labeled antigens with an antiserum against TMP which blocks malaria parasite-induced TNF production. We detected four proteins associated with IMP when the immunoprecipitates were separated by SDS-PAGE and analyzed by autoradiography. To evaluate the capacity of different P. falciparum antigens to induce cytokine production we separated a mixture of exoantigens by SDS-PAGE and purified individual antigen fractions by electroelution from the SDS-PAGE gels. Antigen fractions of 43-71 kDa and of a low molecular mass of <20 kDa contained the dominant inducers of TNF alpha interleukin 1 alpha, and interleukin 6 production from human mononuclear cells. The low-molecular-mass antigen fraction contained hemoglobin, while no parasite-specific proteins were detectable when tested by immunoblotting. Hemoglobin may act as a carrier for cytokine-inducing malaria parasite toxins. (C) 1996 Academic Press