Del-1, an endogenous leukocyte-endothelial adhesion inhibitor, limits inflammatory cell recruitment.
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.
Choi
Eun Young
EY
Experimental Immunology Branch, Center for Cancer Research, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA.
Chavakis
Emmanouil
E
Czabanka
Marcus A
MA
Langer
Harald F
HF
Fraemohs
Line
L
Economopoulou
Matina
M
Kundu
Ramendra K
RK
Orlandi
Alessia
A
Zheng
Ying Yi
YY
Prieto
Darue A
DA
Ballantyne
Christie M
CM
Constant
Stephanie L
SL
Aird
William C
WC
Papayannopoulou
Thalia
T
Gahmberg
Carl G
CG
Udey
Mark C
MC
Vajkoczy
Peter
P
Quertermous
Thomas
T
Dimmeler
Stefanie
S
Weber
Christian
C
Chavakis
Triantafyllos
T
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
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