Studies on protozoan killing mechanisms by eosinophilic leukocytes

用IL-5转基因小鼠(C3H/HEN-TGN(IL-5)IMEG；IL-5TG小鼠)和BALB/c小鼠进行体内和体外实验，研究嗜酸性白细胞对利什曼原虫的杀伤机制。取得了以下研究成果：1.观察到IL-5Tg小鼠感染亚马孙链霉菌后，皮损部位生长和原虫增殖。与C3H/母鸡小鼠相比，差异显著。在IL-4或干扰素-γ存在下，从IL-5TG小鼠分离的嗜酸性白细胞对L.A.原虫有明显的杀灭活性。这种杀伤活性在过氧化氢酶存在的情况下被抑制。由此推测，参与杀灭原生动物的嗜酸性粒细胞的效应分子为H_2O_2.3。嗜酸性白细胞的脱颗粒不参与嗜酸性白细胞的杀灭原虫作用。嗜酸性白细胞的趋化需要原虫物质和IL-4。用IL-5免疫BALB/c小鼠(对利什曼原虫高度敏感)，使嗜酸性粒细胞增多，皮损生长受到抑制，外周血中IL-4和干扰素-γ水平升高。此外，当对这些小鼠进行内毒素治疗时，也变得明显地增强了降压作用。TG小鼠和BALB/c小鼠的嗜酸性白细胞在功能和形态上的差异不被接受。

The Leishmania protozoa killing mechanisms by eosinophilic leukocytes were investigated in vivo and in vitro experiments using IL-5 transgenic mice (C3H/HeN-TgN (IL-5) Imeg ; IL-5 TG mouse) and BALB/c mice. The following results were obtained.1. It was observed that growth of lesion site and protozoan proliferation in the infection site of IL-5 TG mice infected with L. amazonensis (L. a.) were significantly controlled compared with those of C3H/HeN mice.2. Eosinophilic leukocytes separated from IL-5 TG mice showed remarkable killing activity to L. a. protozoa under presence of IL-4 or INF- γ. This killing activity was inhibited under presence of the catalase. From these results, it was thought that the effecter molecule of eosinophils, which participates in L. a. protozoan killing, was H_2O_2.3. The degranulation of the eosinophilic leukocytes was not participating in the protozoan-killing action of the eosinophilic leukocytes.4. The protozoan matter and IL-4 were required for the chemotaxis of the eosinophilic leukocytes.5. The suppression of the growth of lesion and the increase of IL-4 and INF-γ in peripheral blood were observed in BALB/c mice (having a high sensitivity to Leishmania) made to increase the eosinophils by IL-5 inoculation. Furthermore, when LPS treatment was performed to these mice, it also became clear that a depressor effect was reinforced.6. The functional and morphological difference did not accept between the eosinophilic leukocytes of TG mice and the cells of BALB/c mice.