Authors: Alisar Zahr, Pilar Alcaide, Jinling Yang, Alexander Jones, Meredith Gregory, Nathaniel G. dela Paz, Sunita Patel-Hett, Tania Nevers, Adarsha Koirala, Francis W. Luscinskas, Magali Saint-Geniez, Bruce Ksander, Patricia A. D’Amore and Pablo Argüeso
Summary:
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.
Source:
Nature Communications; 7, 10363 (02/02/16)