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
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Research Support, N.I.H., Extramural
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Research Support, N.I.H., Intramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Bronchoalveolar Lavage Fluid / cytology
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Bronchoalveolar Lavage Fluid / immunology
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Calcium-Binding Proteins
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Carrier Proteins / physiology*
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Cell Adhesion Molecules
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Cell Adhesion*
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Endothelial Cells / physiology*
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Intercellular Adhesion Molecule-1 / metabolism
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Intercellular Signaling Peptides and Proteins
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Leukocyte Rolling
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Ligands
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Lipopolysaccharides / immunology
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Lung / blood supply
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Lung / immunology
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Lymphocyte Function-Associated Antigen-1 / metabolism
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Mice
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Monocytes / physiology*
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Neutrophil Infiltration*
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Neutrophils / physiology*
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Peritonitis / immunology
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Pneumonia / immunology*
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Recombinant Fusion Proteins / metabolism
Substances
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Calcium-Binding Proteins
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Carrier Proteins
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Cell Adhesion Molecules
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Edil3 protein, mouse
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Icam1 protein, mouse
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Intercellular Signaling Peptides and Proteins
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Ligands
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Lipopolysaccharides
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Lymphocyte Function-Associated Antigen-1
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Recombinant Fusion Proteins
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Intercellular Adhesion Molecule-1