Hirata Mizuki, Hara Tatsuru, Kage Masayoshi, Fukuma Toshihide, Sendo Fujiro
Department of Parasitology and Department of Pathology, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
Parasite Immunol. 2002 Sep-Oct;24(9-10):479-88. doi: 10.1046/j.1365-3024.2002.00491.x.
The present study was designed to investigate the role of neutrophils during the development of Schistosoma japonicum egg granulomas, in C57BL/6 and CBA mice. Laid eggs were implanted into the liver and monoclonal antibody, RB6-8C5, was used to eliminate neutrophils. After daily antibody treatment between days 9 and 13 of egg implantation, both strains of mice showed a marked decrease in neutrophil infiltration and coagulative hepatocyte necrosis at 2 weeks. At 4 weeks, after antibody administration every other day between days 16 and 26, granuloma formation in C57BL/6 mice was not affected by the treatment, whereas CBA mice exhibited a significant increase of reactions. Neutropenia augmented the Th2 cytokine response (IL-4, IL-13 and IL-5), but not for IFN-gamma at any time point examined and in either strain of mice. Higher levels of IL-4 and IL-13 were noted in CBA mice at early and late stages of granuloma formation, compared to C57BL/6 mice. There was also a striking difference in IL-13 production between the two strains. Our results indicate that neutropenia is associated with a significant augmentation of S. japonicum egg-induced granuloma formation in CBA mice, probably through increase in Th2 cytokines, however, the effects differ between early and late stages and between high and low responders.
本研究旨在探讨中性粒细胞在日本血吸虫虫卵肉芽肿形成过程中的作用,研究对象为C57BL/6和CBA小鼠。将产出的虫卵植入肝脏,并使用单克隆抗体RB6-8C5清除中性粒细胞。在虫卵植入后的第9天至第13天每天进行抗体治疗后,两种品系的小鼠在2周时中性粒细胞浸润和凝固性肝细胞坏死均显著减少。在第16天至第26天每隔一天给予抗体后,在4周时,C57BL/6小鼠的肉芽肿形成不受该治疗影响,而CBA小鼠的反应显著增加。中性粒细胞减少增强了Th2细胞因子反应(IL-4、IL-13和IL-5),但在任何检测时间点,两种品系小鼠的IFN-γ均未受影响。与C57BL/6小鼠相比,CBA小鼠在肉芽肿形成的早期和晚期IL-4和IL-13水平更高。两种品系小鼠在IL-13产生方面也存在显著差异。我们的结果表明,中性粒细胞减少与CBA小鼠中日本血吸虫虫卵诱导的肉芽肿形成显著增加有关,可能是通过Th2细胞因子增加所致,然而,其影响在早期和晚期以及高反应者和低反应者之间有所不同。