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

Science. 2008 Nov 14;322(5904):1101-4. doi: 10.1126/science.1165218.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bronchoalveolar Lavage Fluid / cytology
  • Bronchoalveolar Lavage Fluid / immunology
  • Carrier Proteins / physiology*
  • Cell Adhesion*
  • Endothelial Cells / physiology*
  • Intercellular Adhesion Molecule-1 / metabolism
  • Intercellular Signaling Peptides and Proteins
  • Leukocyte Rolling
  • Ligands
  • Lipopolysaccharides / immunology
  • Lung / blood supply
  • Lung / immunology
  • Lymphocyte Function-Associated Antigen-1 / metabolism
  • Mice
  • Monocytes / physiology*
  • Neutrophil Infiltration*
  • Neutrophils / physiology*
  • Peritonitis / immunology
  • Pneumonia / immunology*
  • Recombinant Fusion Proteins / metabolism

Substances

  • Carrier Proteins
  • Edil3 protein, mouse
  • Icam1 protein, mouse
  • Intercellular Signaling Peptides and Proteins
  • Ligands
  • Lipopolysaccharides
  • Lymphocyte Function-Associated Antigen-1
  • Recombinant Fusion Proteins
  • Intercellular Adhesion Molecule-1