Functional analysis of neutrophils that infiltrated in the S.mansoni-induced hepatic granuloma

曼氏血吸虫病是曼氏血吸虫感染后进展的一种慢性疾病。曼氏血吸虫寄生于门静脉。成虫产生的虫卵在肝脏毛细血管中被栓塞，然后形成肝脏肉芽肿。此外，它最终发展为肝硬变。中性粒细胞被认为在肝肉芽肿的形成中起着重要作用。然后采用曼氏血吸虫感染小鼠动物模型和中性粒细胞清除抗体检测中性粒细胞在肉芽肿形成中的作用。在BALB/c小鼠体内感染60条尾虫。在感染前或感染后7周，就在成虫产卵之前，小鼠被注射大鼠单抗(RB6-8C5)以消除中性粒细胞。感染后8周或9周，取小鼠肝脏进行组织病理学检查，并检测感染小鼠粪便中肿瘤坏死因子-α的产生及成虫和虫卵的数量。尽管注射RB6-8C5能显著降低小鼠外周血中中性粒细胞的数量，但与注射抗体的对照小鼠相比，消除中性粒细胞的小鼠肝肉芽肿的大小、肉芽肿内细胞的渗入、肿瘤坏死因子-α的产生以及粪便中成虫和虫卵的数量均无明显影响。中性粒细胞的瞬时消除可能不足以影响肉芽肿的形成和曼氏葡萄球菌的生长。我们需要通过不同剂量和不同时间的抗体注射进一步检查，以更彻底地清除中性粒细胞。

Schistosomiasis mansoni is a chronic disease progressed after S.mansoni infection. S.mansoni is parasitic in the portal vein. The eggs produced by adult worms are embolized in the hepatic capillary blood vessels and then they form hepatic granulomas. Furthermore it progresses to liver cirrhosis finally. Neutrophils are supposed to have an important role for the hepatic granuloma formation. Then we employed mouse animal model of S.mansoni infection and neutrophil eliminating antibody to examine the functional role of neutrophil on the granuloma formation. 60 cercarias were infected in BALB/c mice intraperitoneally. Before infection or 7 weeks after infection just before egg production from adult worms, mice were injected with rat monoclonal antibody (RB6-8C5) to eliminate neutrophils. 8 or 9 weeks after infection, mouse liver was examined for histophathological examination and TNF-α production or the number of adult worms and eggs in infected mouse feces were checked. Though RB6-8C5 injections reduced the number of peripheral neutrophils dramatically but transiently, the size of formed hepatic granuloma, cells infiltrated in the granuloma, TNF-α production and the number of adult worms and eggs in the feces were not affected in the neutrophil eliminated mice as compared with control antibody injected mice. The transient elimination of neutrophils may not be sufficient to affect the granuloma formation and S.mansoni growth. We need further examinations with different doses and durations of antibody injection to remove neutrophil more completely.