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

约氏疟原虫感染小鼠（感染后7天）的血细胞裂解物显示出强烈的中性粒细胞趋化活性，呈剂量依赖性。时间进程研究显示，红细胞裂解物的中性粒细胞趋化活性在感染红细胞数量增加之前增加。从红细胞裂解液中纯化的NCF的氨基端氨基酸序列分析表明，NCF是一种干扰素诱导蛋白（IP 18）。定位研究表明，中性粒细胞趋化活性的表位存在于分子的中心部分。用抗IP 18的多克隆抗体，对约氏疟原虫感染过程中红细胞上IP 18含量的变化进行了时程研究。约氏疟原虫感染后，正常小鼠红细胞中可检测到少量的IP 18，但其含量明显增加，并在感染后第6天达到高峰。脾细胞中IP18及其mRNA的量也增加。在体外培养的恶性疟原虫中，加入不同浓度的中性粒细胞，IP 18对恶性疟原虫生长的抑制作用与中性粒细胞的浓度有关。当加入泛蛋白代替IP 18时，到目前为止没有观察到对寄生虫生长的抑制。这些结果表明，IP18可能作为一个重要的分子宿主防御系统对疟疾感染。

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.