Sci. Signal., 18 November 2008
Immunology Putting the Brakes on Inflammation
Stella M. Hurtley
Science, AAAS, Cambridge CB2 1LQ, UK
Numerous adhesion receptors of the selectin, integrin, or immunoglobulin family promote inflammatory cell recruitment. In contrast, inhibitors of the leukocyte adhesion cascade are not well known. Now Choi et al. have characterized developmental endothelial locus-1 (Del-1) as an endogenous inhibitor of the leukocyte adhesion cascade. Del-1, which is an endothelially expressed, secreted molecule, is a ligand of the major leukocyte adhesion receptor LFA-1. Soluble Del-1 inhibited neutrophil adhesion under both static and physiologic flow conditions. Endothelial Del-1 deficiency promoted increased leukocyte adhesion, and mice lacking Del-1 displayed significantly higher neutrophil accumulation during lung inflammation, which was reversed in Del-1/LFA-1 double-deficient mice. Thus, Del-1 interacts with LFA-1, preventing inflammatory cell recruitment.
E. Y. Choi, E. Chavakis, M. A. Czabanka, H. F. Langer, L. Fraemohs, M. Economopoulou, R. K. Kundu, A. Orlandi, Y. Y. Zheng, D. A. Prieto, C. M. Ballantyne, S. L. Constant, W. C. Aird, T. Papayannopoulou, C. G. Gahmberg, M. C. Udey, P. Vajkoczy, T. Quertermous, S. Dimmeler, C. Weber, T. Chavakis, Del-1, an endogenous leukocyte-endothelial adhesion inhibitor, limits inflammatory cell recruitment. Science 322, 1101–1104 (2008). [Abstract] [Full Text]
Citation: S. M. Hurtley, Putting the Brakes on Inflammation. Sci. Signal. 1, ec391 (2008).
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