Buscher Konrad, Wang Huiyu, Zhang Xueli, Striewski Paul, Wirth Benedikt, Saggu Gurpanna, Lütke-Enking Stefan, Mayadas Tanya N, Ley Klaus, Sorokin Lydia, Song Jian
Institute of Physiological Chemistry and Pathobiochemistry, University of Muenster, Muenster 48149, Germany.
Cells-in-Motion Cluster of Excellence, University of Muenster, Muenster 48149, Germany.
Nat Commun. 2016 Mar 4;7:10828. doi: 10.1038/ncomms10828.
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 TNFα-, 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.
急性腹膜炎是一种常见的病症，可引发严重脓毒症这一致命并发症。中性粒细胞是感染的第一反应者，但它们向腹腔募集的机制仍不清楚。在此，我们证明，在肿瘤坏死因子α、大肠杆菌以及盲肠结扎和穿刺诱导的炎症模型中，大网膜的高内皮微静脉（HEV）构成了主要的进入途径。中性粒细胞穿过HEV的迁移速度比穿过传统毛细血管后微静脉更快，并且需要一组独特的黏附受体，包括外周淋巴结地址素、E-选择素、L-选择素和Mac-1，但不需要P-选择素或淋巴细胞功能相关抗原-1（LFA-1）。网膜乳斑容易聚集腹腔内的大肠杆菌，巨噬细胞和募集来的中性粒细胞在此协同进行吞噬和杀灭作用。抑制网膜中性粒细胞反应会加剧腹膜炎的脓毒症进展。这些数据表明，HEV是急性腹膜炎中中性粒细胞临床上相关的血管募集部位，对于宿主抵御早期全身性细菌传播和脓毒症至关重要。
