Goto H, Gomes C M, Corbett C E, Monteiro H P, Gidlund M
Department of Preventive Medicine, Instituto de Medicina Tropical de São Paulo (LIM-38), Sao Paulo, Brazil.
Proc Natl Acad Sci U S A. 1998 Oct 27;95(22):13211-6. doi: 10.1073/pnas.95.22.13211.
Leishmaniases are diseases caused by protozoa of the genus Leishmania that affect more than 20 million people in the world. The initial phase of the infection is fundamental for either the progression or control of the disease. The Leishmania parasites are injected in the skin as promastigotes and then, after been phagocytized by the host macrophages, rapidly transform into amastigotes. In this phase different nonspecific cellular and humoral elements participate. We have shown previously that insulin-like growth factor (IGF)-I that is constitutively present in the skin induces growth of Leishmania promastigotes. In the present paper we show further evidence for the importance of this factor: (i) IGF-I also can induce a growth response in Leishmania (Leishmania) mexicana amastigotes; (ii) IGF-I binds specifically to a putative single-site receptor on both promastigotes and amastigotes; (iii) IGF-I induces a rapid tyrosine phosphorylation of parasite proteins with different molecular mass in promastigotes and amastigotes of L. (L.) mexicana; and, finally, (iv) the cutaneous lesion in the mice when challenged by IGF-I-preactivated Leishmania (Viannia) panamensis is increased significantly because of inflammatory process and growth of parasites. We thus suggest that IGF-I is another important host factor participating in the Leishmania-host interplay in the early stage during the establishment of the infection and presumably also in the later stages.
利什曼病是由利什曼原虫属的原生动物引起的疾病,全球有超过2000万人受其影响。感染的初始阶段对于疾病的进展或控制至关重要。利什曼原虫以前鞭毛体的形式注入皮肤,然后在被宿主巨噬细胞吞噬后迅速转变为无鞭毛体。在这个阶段,不同的非特异性细胞和体液成分会参与其中。我们之前已经表明,皮肤中持续存在的胰岛素样生长因子(IGF)-I可诱导利什曼原虫前鞭毛体的生长。在本文中,我们进一步证明了该因子的重要性:(i)IGF-I也能诱导墨西哥利什曼原虫无鞭毛体产生生长反应;(ii)IGF-I特异性结合前鞭毛体和无鞭毛体上的一种假定的单位点受体;(iii)IGF-I诱导墨西哥利什曼原虫前鞭毛体和无鞭毛体中不同分子量的寄生虫蛋白快速酪氨酸磷酸化;最后,(iv)当用IGF-I预激活的巴拿马利什曼原虫攻击小鼠时,由于炎症过程和寄生虫生长,皮肤损伤显著增加。因此,我们认为IGF-I是另一个重要的宿主因子,在感染建立的早期阶段以及可能在后期阶段参与利什曼原虫与宿主的相互作用。