Protection from septic peritonitis by rapid neutrophil recruitment through omental high endothelial venules
Protection from septic peritonitis by rapid neutrophil recruitment through omental high endothelial venules
复制标题
DOI：
10.1038/ncomms10828
复制
发表时间：
2016-03-01
影响因子：
16.6
通讯作者：
Song, Jian
中科院分区：
文献类型：
--
作者：
Buscher, Konrad;Wang, Huiyu;Song, Jian
急性腹膜炎是一种常见的医学疾病，可引发严重脓毒症作为危及生命的并发症。中性粒细胞是感染的第一反应者，但腹腔的募集机制仍不清楚。在这里，我们证明了大网膜的高内皮微静脉（HEVs）构成了TNF α、大肠杆菌（E。大肠杆菌）和盲肠结扎和穿刺诱导的炎症模型。穿过HEV的神经元迁移比穿过常规毛细血管后微静脉快，并且需要一组独特的粘附受体，包括外周淋巴结地址素、E-、L-选择素和Mac-1，但不包括P-选择素或LFA-1。网膜乳斑易集中于腹腔内。其中巨噬细胞和募集的中性粒细胞协作吞噬和杀死。抑制网膜中性粒细胞反应可加重腹膜炎的脓毒性进展。该数据将HEV确定为急性腹膜炎中中性粒细胞的临床相关血管募集部位，其对于宿主防御早期全身细菌扩散和败血症是不可或缺的。
Acute peritonitis is a frequent medical condition that can trigger severe sepsis as a life-threatening complication. Neutrophils are first-responders in infection but recruitment mechanisms to the abdominal cavity remain poorly defined. Here, we demonstrate that high endothelial venules (HEVs) of the greater omentum constitute a main entry pathway in TNF alpha-, Escherichia coli (E. coli)- and caecal ligation and puncture-induced models of inflammation. Neutrophil transmigration across HEVs is faster than across conventional postcapillary venules and requires a unique set of adhesion receptors including peripheral node addressin, E-, L-selectin and Mac-1 but not P-selectin or LFA-1. Omental milky spots readily concentrate intra-abdominal E. coli where macrophages and recruited neutrophils collaborate in phagocytosis and killing. Inhibition of the omental neutrophil response exacerbates septic progression of peritonitis. This data identifies HEVs as a clinically relevant vascular recruitment site for neutrophils in acute peritonitis that is indispensable for host defence against early systemic bacterial spread and sepsis.