期刊
FASEB JOURNAL
卷 35, 期 5, 页码 -出版社
WILEY
DOI: 10.1096/fj.202000662RR
关键词
cytoskeletal remodeling; endothelial integrity; E-selectin; neutrophil; transmigration
资金
- National Natural Science Foundation of China (NSFC) [31627804, 91642203, 11772345, 91539119]
- National Key Rsearch and Development Program of China [2016YFA0501601]
- Chinese Academy of Sciences Strategic Priority Research Program [XDB22040101]
- Frontier Science Key Project [QYZDJ--SSW--JSC018]
E-selectins negatively regulate neutrophil transmigration by altering endothelial plasticity, downregulating cortactin and Arp2/3 activation, and enhancing VE-cadherin adhesive function. The findings also highlight the overlapping functions of redundant P-selectins in neutrophil adhesion and transmigration, contributing to better understanding of actin remodeling and junctional integrity in endothelial cells mediating leukocyte TEM.
Transendothelial migration (TEM) of neutrophils under blood flow is critical in the inflammatory cascade. However, the role of endothelial plasticity in this process is not fully understood. Therefore, we used an in vitro model to test the dynamics of human polymorphonuclear neutrophil (PMN) TEM across lipopolysaccharide-treated human umbilical vein endothelial cell (HUVEC) monolayers. Interestingly, shRNA-E-selectin knockdown in HUVECs destabilized endothelial junctional integrity by reducing actin branching and increasing stress fiber at cell-cell junctions. This process is accomplished by downregulating the activation of cortactin and Arp2/3, which in turn alters the adhesive function of VE-cadherin, enhancing PMN transmigration. Meanwhile, redundant P-selectins possess overlapping functions in E-selectin-mediated neutrophil adhesion, and transmigration. These results demonstrate, to our knowledge, for the first time, that E-selectins negatively regulate neutrophil transmigration through alterations in endothelial plasticity. Furthermore, it improves our understanding of the mechanisms underlying actin remodeling, and junctional integrity, in endothelial cells mediating leukocyte TEM.
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