Division of Biology, Kansas State University, Manhattan, KS 66506, USA.
Shock. 2011 Feb;35(2):134-40. doi: 10.1097/SHK.0b013e3181ed8ec9.
Hemorrhage and hemorrhagic shock instigate intestinal damage and inflammation. Multiple components of the innate immune response, including complement and neutrophil infiltration, are implicated in this pathology. To investigate the interaction of complement activation and other components of the innate immune response during hemorrhage, we treated mice after hemorrhage with CR2-fH, a targeted inhibitor of the alternative complement pathway and assessed intestinal damage and inflammation 2 h after hemorrhage. In wild-type mice, CR2-fH attenuated hemorrhage-induced, midjejunal damage and inflammation as determined by decreased mucosal damage, macrophage infiltration, leukotriene B4, IL-12p40, and TNF-[alpha] production. The critical nature of intestinal macrophage infiltration and activation in the response to hemorrhage was further determined using mice pretreated with clodronate-containing liposomes. The absence of either macrophages or IL-12p70 attenuated intestinal damage. These data suggest that complement activation and macrophage infiltration with IL-12p70 production are critical to hemorrhage-induced midjejunal damage and inflammation.
出血和失血性休克会引发肠道损伤和炎症。先天免疫反应的多个组成部分，包括补体和中性粒细胞浸润，都与这种病理学有关。为了研究补体激活和先天免疫反应的其他成分在出血期间的相互作用，我们在用 CR2-fH 处理出血后的小鼠后，评估了出血后 2 小时的肠道损伤和炎症。在野生型小鼠中，CR2-fH 减轻了出血引起的空肠中段损伤和炎症，表现为粘膜损伤、巨噬细胞浸润、白三烯 B4、IL-12p40 和 TNF-α产生减少。使用含有氯膦酸盐的脂质体预处理的小鼠进一步确定了肠道巨噬细胞浸润和激活在出血反应中的关键作用。巨噬细胞或 IL-12p70 的缺失均减轻了肠道损伤。这些数据表明，补体激活和巨噬细胞浸润以及 IL-12p70 的产生对出血引起的空肠中段损伤和炎症至关重要。
