Yipp Bryan G, Kim Jung Hwan, Lima Ronald, Zbytnuik Lori D, Petri Björn, Swanlund Nick, Ho May, Szeto Vivian G, Tak Tamar, Koenderman Leo, Pickkers Peter, Tool Anton T J, Kuijpers Taco W, van den Berg Timo K, Looney Mark R, Krummel Matthew F, Kubes Paul
Department of Critical Care, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
Calvin, Phoebe and Joan Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
Sci Immunol. 2017 Apr 28;2(10). doi: 10.1126/sciimmunol.aam8929.
Bloodstream infection is a hallmark of sepsis, a medically emergent condition requiring rapid treatment. However, upregulation of host defense proteins through toll-like receptors and NFκB requires hours after endotoxin detection. Using confocal pulmonary intravital microscopy, we identified that the lung provides a TLR4-Myd88-and abl tyrosine kinase-dependent niche for immediate CD11b-dependent neutrophil responses to endotoxin and Gram-negative bloodstream pathogens. In an model of bacteremia, neutrophils crawled to and rapidly phagocytosed sequestered to the lung endothelium. Therefore, the lung capillaries provide a vascular defensive niche whereby endothelium and neutrophils cooperate for immediate detection and capture of disseminating pathogens.
血流感染是脓毒症的一个标志，脓毒症是一种需要迅速治疗的医学急症。然而，通过Toll样受体和NFκB上调宿主防御蛋白在内毒素检测后需要数小时。利用共聚焦肺活体显微镜，我们发现肺为Toll样受体4（TLR4）-髓样分化因子88（Myd88）和abl酪氨酸激酶依赖性小生境提供了条件，使得中性粒细胞能对内皮毒素和革兰氏阴性血流病原体立即产生依赖于CD11b的反应。在菌血症模型中，中性粒细胞爬行至并迅速吞噬隔离于肺内皮的（病原体）。因此，肺毛细血管提供了一个血管防御小生境，通过它内皮细胞和中性粒细胞协作以立即检测并捕获播散的病原体。
