Monocytic thrombomodulin promotes cell adhesion through interacting with its ligand, Lewis y

Wei Ling Lin, Chia Chi Chen, Guey Yueh Shi, Chih Yuan Ma, Chuan Fa Chang, Hua Lin Wu

研究成果: Article同行評審

9 引文 斯高帕斯(Scopus)


The leukocyte adhesion cascade involves multiple events that efficiently localize circulating leukocytes into the injured sites to mediate inflammatory responses. From rolling to firm adhesion, the interactions between adhesion molecules have pivotal roles in increasing the avidity of leukocytes to endothelial cells. Thrombomodulin (TM), an essential anticoagulant protein in the vasculature, is also expressed on leukocytes. We previously demonstrated that Lewis y (Le y), a specific ligand of TM, is upregulated in inflamed endothelium and is involved in leukocyte adhesion. The current study aimed to investigate whether leukocyte-expressed TM promotes cell adhesion by interacting with Le y. Using human monocytic THP-1 cells as an in vitro cell model, we showed that TM increases THP-1 cell adhesion to inflamed endothelium as well as to Le y -immobilized surface. When THP-1 adhered to activated endothelium and Le y -immobilized surface, the TM distribution became polarized. Addition of soluble Le y to a suspension of THP-1 cells with TM expression triggered an increase in the level of phosphorylated p38 mitogen-activated protein kinase (MAPK), which enabled THP-1 to adhere firmly to intercellular adhesion molecule (ICAM)-1 by activating β 2 integrins. In vivo, macrophage infiltration and neointima formation following arterial ligation-induced vascular injury were higher in wild-type TM (TM flox/flox) than in myeloid-specific TM-deficient (LysMcre/TM flox/flox) mice. Taken together, these results suggest a novel function for TM as an adhesion molecule in monocytes, where it enhances cell adhesion by binding Le y, leading to β 2 integrin activation via p38 MAPK.

頁(從 - 到)372-379
期刊Immunology and Cell Biology
出版狀態Published - 2017 4月 1

All Science Journal Classification (ASJC) codes

  • 免疫學和過敏
  • 免疫學
  • 細胞生物學


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