<br>LFA-1 (CD11a/CD18) 和 Mac-1 (CD11b/CD18) 通过热点 I 和 II 明显调节中性粒细胞外渗。,Experimental & Molecular Medicine

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LFA-1 (CD11a/CD18) 和 Mac-1 (CD11b/CD18) 通过热点 I 和 II 明显调节中性粒细胞外渗。
Experimental & Molecular Medicine ( IF 9.5 ) Pub Date : 2019-04-09 , DOI: 10.1038/s12276-019-0227-1
Young-Min Hyun _{1,

2} , Young Ho Choe _{1,

2} , Sang A Park _{1,

2,

3} , Minsoo Kim ₄

Affiliation

白细胞外渗的精确时空调节是对损伤或感染产生有效免疫反应的关键。整合素 LFA-1(CD11a/CD18) 和 Mac-1(CD11b/CD18) 在中性粒细胞迁移中发挥重叠作用，因为它们响应细胞外信号传导而结合相同和不同的配体。使用双光子活体成像和透射电子显微镜，我们通过阐明独特的作用，观察到中性粒细胞外渗过程中中性粒细胞进入内皮细胞单层并从基底膜和周细胞鞘退出的首选位点的存在，即热点I和II。 LFA-1 和 Mac-1。为了穿透血管内皮，中性粒细胞必须首先通过热点I（即进入内皮的点）穿透内皮细胞层。中性粒细胞经常在内皮细胞层和基底膜之间的间隙中停留较长时间（>20 分钟）。随后，中性粒细胞在热点II处穿透基底膜和周细胞鞘，这是离开血管内皮的最后阶段。为了进一步研究LFA-1和Mac-1的作用，我们新生成了LFA-1 FRET (CD11a-YFP/CD18-CFP)小鼠和Mac-1 FRET (CD11b-YFP/CD18-CFP)小鼠。使用两只 FRET 小鼠，我们能够确定 LFA-1 和 Mac-1 明显调节中性粒细胞外渗级联。我们的数据表明，血管内皮在中性粒细胞外渗过程中起到双层屏障的作用。我们认为，中性粒细胞通过热点 I 和 II 穿过内皮的协调调节可能对于炎症期间血管稳态至关重要。

"点击查看英文标题和摘要"

LFA-1 (CD11a/CD18) and Mac-1 (CD11b/CD18) distinctly regulate neutrophil extravasation through hotspots I and II.

Precise spatiotemporal regulation of leukocyte extravasation is key for generating an efficient immune response to injury or infection. The integrins LFA-1(CD11a/CD18) and Mac-1(CD11b/CD18) play overlapping roles in neutrophil migration because they bind the same as well as different ligands in response to extracellular signaling. Using two-photon intravital imaging and transmission electron microscopy, we observed the existence of preferred sites for neutrophil entrance into the endothelial cell monolayer and exit from the basement membrane and pericyte sheath during neutrophil extravasation, namely, hotspots I and II, by elucidating distinctive roles of LFA-1 and Mac-1. To penetrate the vascular endothelium, neutrophils must first penetrate the endothelial cell layer through hotspot I (i.e., the point of entry into the endothelium). Neutrophils frequently remain in the space between the endothelial cell layer and the basement membrane for a prolonged period (>20 min). Subsequently, neutrophils penetrate the basement membrane and pericyte sheath at hotspot II, which is the final stage of exiting the vascular endothelium. To further investigate the roles of LFA-1 and Mac-1, we newly generated LFA-1 FRET (CD11a-YFP/CD18-CFP) mice and Mac-1 FRET (CD11b-YFP/CD18-CFP) mice. Using both FRET mice, we were able to determine that LFA-1 and Mac-1 distinctly regulate the neutrophil extravasation cascade. Our data suggest that the vascular endothelium functions as a double-layered barrier in the steps of neutrophil extravasation. We propose that the harmonized regulation of neutrophil penetration through the endothelium via hotspots I and II may be critical for vascular homeostasis during inflammation.

更新日期：2019-05-16

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