title: Del-1, an endogenous leukocyte-endothelial adhesion inhibitor, limits inflammatory cell recruitment.
abstract: Leukocyte recruitment to sites of infection or inflammation requires multiple adhesive events. Although numerous players promoting leukocyte-endothelial interactions have been characterized, functionally important endogenous inhibitors of leukocyte adhesion have not been identified. Here we describe the endothelially derived secreted molecule Del-1 (developmental endothelial locus-1) as an anti-adhesive factor that interferes with the integrin LFA-1-dependent leukocyte-endothelial adhesion. Endothelial Del-1 deficiency increased LFA-1-dependent leukocyte adhesion in vitro and in vivo. Del-1-/- mice displayed significantly higher neutrophil accumulation in lipopolysaccharide-induced lung inflammation in vivo, which was reversed in Del-1/LFA-1 double-deficient mice. Thus, Del-1 is an endogenous inhibitor of inflammatory cell recruitment and could provide a basis for targeting leukocyte-endothelial interactions in disease.
authors.affiliation: Experimental Immunology Branch, Center for Cancer Research, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA.
authors.forename: Eun Young
authors.initials: EY
authors.lastname: Choi
authors.forename: Emmanouil
authors.initials: E
authors.lastname: Chavakis
authors.forename: Marcus A
authors.initials: MA
authors.lastname: Czabanka
authors.forename: Harald F
authors.initials: HF
authors.lastname: Langer
authors.forename: Line
authors.initials: L
authors.lastname: Fraemohs
authors.forename: Matina
authors.initials: M
authors.lastname: Economopoulou
authors.forename: Ramendra K
authors.initials: RK
authors.lastname: Kundu
authors.forename: Alessia
authors.initials: A
authors.lastname: Orlandi
authors.forename: Ying Yi
authors.initials: YY
authors.lastname: Zheng
authors.forename: Darue A
authors.initials: DA
authors.lastname: Prieto
authors.forename: Christie M
authors.initials: CM
authors.lastname: Ballantyne
authors.forename: Stephanie L
authors.initials: SL
authors.lastname: Constant
authors.forename: William C
authors.initials: WC
authors.lastname: Aird
authors.forename: Thalia
authors.initials: T
authors.lastname: Papayannopoulou
authors.forename: Carl G
authors.initials: CG
authors.lastname: Gahmberg
authors.forename: Mark C
authors.initials: MC
authors.lastname: Udey
authors.forename: Peter
authors.initials: P
authors.lastname: Vajkoczy
authors.forename: Thomas
authors.initials: T
authors.lastname: Quertermous
authors.forename: Stefanie
authors.initials: S
authors.lastname: Dimmeler
authors.forename: Christian
authors.initials: C
authors.lastname: Weber
authors.forename: Triantafyllos
authors.initials: T
authors.lastname: Chavakis
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins / Q000502:physiology*; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules; D042783:Endothelial Cells / Q000502:physiology*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins; D036904:Leukocyte Rolling; D008024:Ligands; D008070:Lipopolysaccharides / Q000276:immunology; D008168:Lung / Q000098:blood supply / Q000276:immunology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism; D051379:Mice; D009000:Monocytes / Q000502:physiology*; D020556:Neutrophil Infiltration; D009504:Neutrophils / Q000502:physiology*; D010538:Peritonitis / Q000276:immunology; D011014:Pneumonia / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000378:metabolism
chemical_list: D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; C491706:Edil3 protein, mouse; C090509:Icam1 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D008024:Ligands; D008070:Lipopolysaccharides; D016169:Lymphocyte Function-Associated Antigen-1; D011993:Recombinant Fusion Proteins; D018799:Intercellular Adhesion Molecule-1