Del-1, an Endogenous Leukocyte-Endothelial Adhesion Inhibitor, Limits Inflammatory Cell Recruitment

• Published in: Science (American Association for the Advancement of Science) 2008-11, Vol.322 (5904), p.1101-1104
• Main Authors: Choi, Eun Young, Chavakis, Emmanouil, Czabanka, Marcus A, Langer, Harald F, Fraemohs, Line, Economopoulou, Matina, Kundu, Ramendra K, Orlandi, Alessia, Zheng, Ying Yi, Prieto, DaRue A, Ballantyne, Christie M, Constant, Stephanie L, Aird, William C, Papayannopoulou, Thalia, Gahmberg, Carl G, Udey, Mark C, Vajkoczy, Peter, Quertermous, Thomas, Dimmeler, Stefanie, Weber, Christian, Chavakis, Triantafyllos
• Format: Article
• Language: English
• Subjects: Animals; Antibodies; Biological and medical sciences; Bronchoalveolar Lavage Fluid - cytology; Bronchoalveolar Lavage Fluid - immunology; Calcium-Binding Proteins; Carrier Proteins - physiology; Cell Adhesion; Cell adhesion & migration; Cell Adhesion Molecules; Cellular biology; Endothelial cells; Endothelial Cells - physiology; Fundamental and applied biological sciences. Psychology; Inflammation; Inflammatory diseases; Inhibitor drugs; Intercellular Adhesion Molecule-1 - metabolism; Intercellular Signaling Peptides and Proteins; Intravenous injections; Leukocyte Rolling; Leukocytes; Ligands; Lipopolysaccharides - immunology; Lung - blood supply; Lung - immunology; Lungs; Lymphocyte Function-Associated Antigen-1 - metabolism; Messenger RNA; Mice; Molecular and cellular biology; Monocytes - physiology; Neutrophil Infiltration; Neutrophils; Neutrophils - physiology; Peritonitis - immunology; Pneumonia - immunology; Recombinant Fusion Proteins - metabolism
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1165218

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.