Endomucin prevents leukocyte-endothelial cell adhesion and has a critical role under resting and inflammatory conditions

Nat Commun. 2016 Feb 2;7:10363. doi: 10.1038/ncomms10363.

Abstract

Endomucin is a membrane-bound glycoprotein expressed luminally by endothelial cells that line postcapillary venules, a primary site of leukocyte recruitment during inflammation. Here we show that endomucin abrogation on quiescent endothelial cells enables neutrophils to adhere firmly, via LFA-1-mediated binding to ICAM-1 constitutively expressed by endothelial cells. Moreover, TNF-α stimulation downregulates cell surface expression of endomucin concurrent with increased expression of adhesion molecules. Adenovirus-mediated expression of endomucin under inflammatory conditions prevents neutrophil adhesion in vitro and reduces the infiltration of CD45(+) and NIMP-R14(+) cells in vivo. These results indicate that endomucin prevents leukocyte contact with adhesion molecules in non-inflamed tissues and that downregulation of endomucin is critical to facilitate adhesion of leukocytes into inflamed tissues.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Animals
  • Cell Adhesion / physiology*
  • Endothelial Cells / physiology*
  • Female
  • Gene Expression Regulation / physiology
  • Humans
  • Inflammation / metabolism*
  • Intercellular Adhesion Molecule-1 / genetics
  • Intercellular Adhesion Molecule-1 / metabolism
  • Leukocytes / physiology*
  • Lymphocyte Function-Associated Antigen-1 / genetics
  • Lymphocyte Function-Associated Antigen-1 / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Neutrophils
  • RNA, Small Interfering
  • Sialomucins / genetics
  • Sialomucins / metabolism*
  • Skin / cytology
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Lymphocyte Function-Associated Antigen-1
  • RNA, Small Interfering
  • Sialomucins
  • Tumor Necrosis Factor-alpha
  • Intercellular Adhesion Molecule-1