Putting the Brakes on Inflammation

Science Signaling  18 Nov 2008:
Vol. 1, Issue 46, pp. ec391
DOI: 10.1126/scisignal.146ec391

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]