A novel neutrophil chemotactic cytokine : identification and functional characterization in malaria

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Blood cell lysate from Plasmodium yoelii infected mice (7 days post-infection) showed an intense neutrophil chemotactic activity in dose-dependent fashion. Time course study revealed that the neutrophil chemotactic activity of the red cell lysate increased prior to the increase the number of infected erythrocytes. Sequence analysis of NH_2-terminal amino acid of the purified NCF from red blood cell lysate showed that the NCF is a kind of interferon-induced protein (IP18). Mapping study indicates that the epitope for neutrophil chemotactic activity exists on the central part of the molecule. Using a polyclonal antibody to IP18, time course study was performed for detecting the change of the amount of IP18 on red blood cells during the P.yoelii infection. Although slight amount of IP18 was detectable on RBC from normal mouse, the amount of IP18 was remarkably increased and peaked at day 6 after P.yoelii infection. The amount of IP18 and its mRNA was also increased in splenocytes. When IP18 was added in the culture system of P.falciparum in the presence of various concentrations of neutrophils in vitro, the parasite growth was inhibited in dose dependent fashion of neutrophils. When ubiquitin was added instead of IP18, no inhibition of the parasite growth was observed so far as examined. These results indicate that IP18 likely acts as an important molecule for the host defense system against malaria infection.