title: Endomucin prevents leukocyte-endothelial cell adhesion and has a critical role under resting and inflammatory conditions.
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.
authors.affiliation: Schepens Eye Research Institute/Massachusetts Eye and Ear and Department of Ophthalmology, Harvard Medical School, 20 Staniford Street, Boston, Massachusetts 02114, USA.
authors.forename: Alisar
authors.initials: A
authors.lastname: Zahr
authors.affiliation: Brigham and Women's Hospital, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.
authors.forename: Pilar
authors.initials: P
authors.lastname: Alcaide
authors.affiliation: Schepens Eye Research Institute/Massachusetts Eye and Ear and Department of Ophthalmology, Harvard Medical School, 20 Staniford Street, Boston, Massachusetts 02114, USA.
authors.forename: Jinling
authors.initials: J
authors.lastname: Yang
authors.affiliation: Schepens Eye Research Institute/Massachusetts Eye and Ear and Department of Ophthalmology, Harvard Medical School, 20 Staniford Street, Boston, Massachusetts 02114, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Jones
authors.affiliation: Schepens Eye Research Institute/Massachusetts Eye and Ear and Department of Ophthalmology, Harvard Medical School, 20 Staniford Street, Boston, Massachusetts 02114, USA.
authors.forename: Meredith
authors.initials: M
authors.lastname: Gregory
authors.affiliation: Schepens Eye Research Institute/Massachusetts Eye and Ear and Department of Ophthalmology, Harvard Medical School, 20 Staniford Street, Boston, Massachusetts 02114, USA.
authors.forename: Nathaniel G
authors.initials: NG
authors.lastname: dela Paz
authors.affiliation: Schepens Eye Research Institute/Massachusetts Eye and Ear and Department of Ophthalmology, Harvard Medical School, 20 Staniford Street, Boston, Massachusetts 02114, USA.
authors.forename: Sunita
authors.initials: S
authors.lastname: Patel-Hett
authors.affiliation: Brigham and Women's Hospital, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.
authors.forename: Tania
authors.initials: T
authors.lastname: Nevers
authors.affiliation: Schepens Eye Research Institute/Massachusetts Eye and Ear and Department of Ophthalmology, Harvard Medical School, 20 Staniford Street, Boston, Massachusetts 02114, USA.
authors.forename: Adarsha
authors.initials: A
authors.lastname: Koirala
authors.affiliation: Brigham and Women's Hospital, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.
authors.forename: Francis W
authors.initials: FW
authors.lastname: Luscinskas
authors.affiliation: Schepens Eye Research Institute/Massachusetts Eye and Ear and Department of Ophthalmology, Harvard Medical School, 20 Staniford Street, Boston, Massachusetts 02114, USA.
authors.forename: Magali
authors.initials: M
authors.lastname: Saint-Geniez
authors.affiliation: Schepens Eye Research Institute/Massachusetts Eye and Ear and Department of Ophthalmology, Harvard Medical School, 20 Staniford Street, Boston, Massachusetts 02114, USA.
authors.forename: Bruce
authors.initials: B
authors.lastname: Ksander
authors.affiliation: Schepens Eye Research Institute/Massachusetts Eye and Ear and Department of Ophthalmology, Harvard Medical School, 20 Staniford Street, Boston, Massachusetts 02114, USA.|Department of Pathology, Harvard Medical School, 25 Shattuck Street, Boston, Massachusetts 02115, USA.
authors.forename: Patricia A
authors.initials: PA
authors.lastname: D'Amore
authors.affiliation: Schepens Eye Research Institute/Massachusetts Eye and Ear and Department of Ophthalmology, Harvard Medical School, 20 Staniford Street, Boston, Massachusetts 02114, USA.
authors.forename: Pablo
authors.initials: P
authors.lastname: Argüeso
mesh_terms: D000368:Aged; D000818:Animals; D002448:Cell Adhesion / Q000502:physiology*; D042783:Endothelial Cells / Q000502:physiology*; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D007962:Leukocytes / Q000502:physiology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils; D034741:RNA, Small Interfering; D052116:Sialomucins / Q000235:genetics / Q000378:metabolism*; D012867:Skin / Q000166:cytology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D016169:Lymphocyte Function-Associated Antigen-1; D034741:RNA, Small Interfering; D052116:Sialomucins; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1
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