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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.

Pubmed ID: 19008446


  • Choi EY
  • Chavakis E
  • Czabanka MA
  • Langer HF
  • Fraemohs L
  • Economopoulou M
  • Kundu RK
  • Orlandi A
  • Zheng YY
  • Prieto DA
  • Ballantyne CM
  • Constant SL
  • Aird WC
  • Papayannopoulou T
  • Gahmberg CG
  • Udey MC
  • Vajkoczy P
  • Quertermous T
  • Dimmeler S
  • Weber C
  • Chavakis T


Science (New York, N.Y.)

Publication Data

November 14, 2008

Associated Grants

  • Agency: NIAID NIH HHS, Id: AI067254
  • Agency: NHLBI NIH HHS, Id: R01 HL082927
  • Agency: Intramural NIH HHS, Id: Z01 BC010790-01

Mesh Terms

  • Animals
  • Bronchoalveolar Lavage Fluid
  • Carrier Proteins
  • Cell Adhesion
  • Endothelial Cells
  • Intercellular Adhesion Molecule-1
  • Leukocyte Rolling
  • Ligands
  • Lipopolysaccharides
  • Lung
  • Lymphocyte Function-Associated Antigen-1
  • Mice
  • Monocytes
  • Neutrophil Infiltration
  • Neutrophils
  • Peritonitis
  • Pneumonia
  • Recombinant Fusion Proteins