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

2008; American Association for the Advancement of Science; Volume: 322; Issue: 5904 Linguagem: Inglês

10.1126/science.1165218

1095-9203

Eun Young Choi, Emmanouil Chavakis, Marcus Czabanka, Harald F. Langer, Line Fraemohs, Matina Economopoulou, Ramendra K. Kundu, Alessia Orlandi, Ying Zheng, DaRue A. Prieto, Christie M. Ballantyne, Stephanie L. Constant, William C. Aird, Thalia Papayannopoulou, Carl G. Gahmberg, Mark C. Udey, Peter Vajkoczy, Thomas Quertermous, Stefanie Dimmeler, Christian Weber, Triantafyllos Chavakis,

Platelet Disorders and Treatments

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.