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

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 ()
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Alisar Zahr: Harvard Medical School
Pilar Alcaide: Brigham and Women’s Hospital, Harvard Medical School
Jinling Yang: Harvard Medical School
Alexander Jones: Harvard Medical School
Meredith Gregory: Harvard Medical School
Nathaniel G. dela Paz: Harvard Medical School
Sunita Patel-Hett: Harvard Medical School
Tania Nevers: Brigham and Women’s Hospital, Harvard Medical School
Adarsha Koirala: Harvard Medical School
Francis W. Luscinskas: Brigham and Women’s Hospital, Harvard Medical School
Magali Saint-Geniez: Harvard Medical School
Bruce Ksander: Harvard Medical School
Patricia A. D’Amore: Harvard Medical School
Pablo Argüeso: Harvard Medical School

Nature Communications, 2016, vol. 7, issue 1, 1-10

Abstract: 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.

Date: 2016
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DOI: 10.1038/ncomms10363

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