Harris F E, Turner D R, Oliveira D B
Division of Renal Medicine, St. George's Hospital Medical School, London, UK.
Int J Exp Pathol. 1999 Jun;80(3):133-42. doi: 10.1046/j.1365-2613.1999.00113.x.
In the Brown Norway rat, mercuric chloride (HgCl2) induces an autoimmune syndrome characterized by necrotizing vasculitis, predominantly affecting the caecum, and a polyclonal B-cell response. The time course of vasculitis is biphasic, with an alphabeta T-cell independent phase occurring within 24 h, and a T-cell and neutrophil dependent phase, maximal at two weeks. The pathogenesis of the early phase of vasculitis is unclear, and this study aims to examine the role of neutrophils. Rat neutrophils were depleted using cyclophosphamide. RP3, an antirat neutrophil monoclonal antibody, inhibited neutrophil leucocytosis but did not deplete neutrophils. Vasculitis was induced by subcutaneous HgCl2 injection. Serial measurements of peripheral blood leucocyte count were made. Rats were killed after 24 or 72 h. The macroscopic appearance of the caecum was scored by an experienced observer, and samples taken for histological examination. Caecums were excised and myeloperoxidase, a marker enzyme for neutrophil infiltration, assayed. Cyclophosphamide induced marked neutropaenia whereas RP3 inhibited the neutrophilia observed after HgCl2 injection. Vasculitis was present in both treated and control animals, with no significant differences in macroscopic or microscopic scores between the groups. Tissue myeloperoxidase activity was low in all animals and did not differ significantly between groups. The data do not support a role for neutrophils in the initial pathogenesis of vasculitis in this model.
在棕色挪威大鼠中,氯化汞(HgCl2)可诱发一种自身免疫综合征,其特征为坏死性血管炎,主要累及盲肠,并伴有多克隆B细胞反应。血管炎的病程呈双相性,在24小时内出现一个αβ T细胞非依赖性阶段,以及一个T细胞和中性粒细胞依赖性阶段,在两周时达到峰值。血管炎早期阶段的发病机制尚不清楚,本研究旨在探讨中性粒细胞的作用。使用环磷酰胺使大鼠中性粒细胞减少。抗大鼠中性粒细胞单克隆抗体RP3可抑制中性粒细胞增多,但不会使中性粒细胞减少。通过皮下注射HgCl2诱发血管炎。连续测量外周血白细胞计数。在24或72小时后处死大鼠。由经验丰富的观察者对盲肠的宏观外观进行评分,并采集样本进行组织学检查。切除盲肠并检测髓过氧化物酶,这是一种用于检测中性粒细胞浸润的标记酶。环磷酰胺可诱发明显的中性粒细胞减少,而RP3可抑制HgCl2注射后观察到的中性粒细胞增多。治疗组和对照组动物均出现血管炎,两组之间的宏观或微观评分无显著差异。所有动物的组织髓过氧化物酶活性均较低,且组间无显著差异。这些数据不支持中性粒细胞在该模型中血管炎初始发病机制中发挥作用。