Bradfield Paul F, Johnson-Léger Caroline A, Zimmerli Claudia, Imhof Beat A
Department of Pathology and Immunology, University Medical Centre, 1 Rue Michel-Servet, CH-1211 Geneva 4, Switzerland.
Int Immunol. 2008 Feb;20(2):247-57. doi: 10.1093/intimm/dxm136. Epub 2007 Dec 21.
One of the key components of the innate immune response is the recognition of microbial products such as LPS by Toll-like receptors on monocytes and neutrophils. We show here that short-term stimulation of primary human monocytes with LPS led to an increase in adhesion of monocytes to endothelial cells and a dramatic decrease in transendothelial migration under static conditions. In contrast, under normal physiological flow, monocyte adhesion and migration across a human umbilical vein endothelial cell monolayer appeared to be unaffected by LPS treatment. LPS stimulation of monocytes activated beta(1) and beta(2) integrins, but did not increase their surface expression levels. During septic shock, reduction in blood flow as a result of vasodilation and vascular permeability leads to adhesion and accumulation of LPS-stimulated circulating monocytes onto the blood vessel walls. The different findings of monocyte migration under static and flow conditions in our study may offer one explanation for this phenomenon. The rapid engagement of LPS-activated monocytes preventing transendothelial migration could represent a novel mechanism of bacterial exclusion from the vasculature. This occurs during the early stages of sepsis, and in turn may modulate the severity of the pathophysiology.
固有免疫反应的关键组成部分之一是单核细胞和中性粒细胞上的Toll样受体对诸如脂多糖（LPS）等微生物产物的识别。我们在此表明，用LPS对原代人单核细胞进行短期刺激会导致在静态条件下单核细胞与内皮细胞的黏附增加以及跨内皮迁移显著减少。相比之下，在正常生理血流条件下，LPS处理似乎不会影响单核细胞对人脐静脉内皮细胞单层的黏附和迁移。LPS刺激单核细胞会激活β1和β2整合素，但不会增加它们的表面表达水平。在脓毒性休克期间，血管舒张和血管通透性导致的血流减少会致使LPS刺激的循环单核细胞黏附并积聚在血管壁上。我们研究中关于单核细胞在静态和血流条件下迁移的不同发现可能为这一现象提供一种解释。LPS激活的单核细胞快速结合从而阻止跨内皮迁移可能代表了一种将细菌排除在脉管系统之外的新机制。这发生在脓毒症的早期阶段，进而可能调节病理生理学的严重程度。
