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E‐selectin negatively regulates polymorphonuclear neutrophil transmigration through altered endothelial junction integrity
Author(s) -
Huang Dandan,
Ding Qihan,
Chen Shenbao,
Lü Shouqin,
Zhang Yan,
Long Mian
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.202000662rr
Subject(s) - microbiology and biotechnology , granulocyte , chemistry , p selectin , l selectin , immunology , biology , cell adhesion molecule , platelet , platelet activation
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.