Shaw M K
International Laboratory for Research on Animal Diseases, Nairobi, Kenya.
Exp Parasitol. 1996 Dec;84(3):344-54. doi: 10.1006/expr.1996.0123.
Theileria parva sporozoites rapidly enter bovine lymphocytes. Since lymphocytes are normally nonphagocytes sporozoite binding to the host cell surface must initiate events in the host cell, leading to the internalization of the parasite. In the present study inhibitors of various key molecules in cell signal transduction and activation pathways, in combination with a method of quantitation, have been used to examine the possible role(s) of these systems in sporozoite entry. A variety of protein kinase inhibitors caused significant inhibition of sporozoite entry. Moreover, protein kinase activities in both the sporozoite and the host cell were essential to sporozoite invasion. Down-regulation of lymphocyte protein kinase C and inhibitors of phospholipase C but not phospholipase A2 activity also blocked sporozoite entry. Parasite entry could also be blocked by inhibitors of G protein activity. Treatment of sporozoites with AIF(3-5) blocked parasite binding while treatment of host cells inhibited sporozoite internalization. Furthermore, sporozoite entry was dependent on a cholera toxin-inhibitable process(es), whereas mastroparan and pertussis toxin had no significant inhibitory effects. Collectively these results provide initial evidence for both parasite protein kinase- and G protein-dependent processes as well as the participation of a variety of host cell signal transduction pathways in the sporozoite entry process.
微小泰勒虫裂殖子能迅速进入牛淋巴细胞。由于淋巴细胞通常不是吞噬细胞，裂殖子与宿主细胞表面的结合必定会引发宿主细胞内的一系列事件，从而导致寄生虫的内化。在本研究中，细胞信号转导和激活途径中各种关键分子的抑制剂，结合一种定量方法，已被用于研究这些系统在裂殖子进入过程中可能发挥的作用。多种蛋白激酶抑制剂对裂殖子的进入有显著抑制作用。此外，裂殖子和宿主细胞中的蛋白激酶活性对于裂殖子的入侵都是必不可少的。淋巴细胞蛋白激酶C的下调以及磷脂酶C而非磷脂酶A2活性的抑制剂也能阻断裂殖子的进入。G蛋白活性的抑制剂也能阻断寄生虫的进入。用AIF(3 - 5)处理裂殖子可阻断寄生虫的结合，而处理宿主细胞则抑制裂殖子的内化。此外，裂殖子的进入依赖于霍乱毒素可抑制的过程，而mastoparan和百日咳毒素没有显著的抑制作用。这些结果共同为寄生虫蛋白激酶和G蛋白依赖的过程以及多种宿主细胞信号转导途径参与裂殖子进入过程提供了初步证据。
