Publication Date:
2008-11-15
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2753175/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2753175/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Choi, Eun Young -- Chavakis, Emmanouil -- Czabanka, Marcus A -- Langer, Harald F -- Fraemohs, Line -- Economopoulou, Matina -- Kundu, Ramendra K -- Orlandi, Alessia -- Zheng, Ying Yi -- Prieto, Darue A -- Ballantyne, Christie M -- Constant, Stephanie L -- Aird, William C -- Papayannopoulou, Thalia -- Gahmberg, Carl G -- Udey, Mark C -- Vajkoczy, Peter -- Quertermous, Thomas -- Dimmeler, Stefanie -- Weber, Christian -- Chavakis, Triantafyllos -- AI067254/AI/NIAID NIH HHS/ -- R01 HL082927/HL/NHLBI NIH HHS/ -- Z01 BC010790-01/Intramural NIH HHS/ -- New York, N.Y. -- Science. 2008 Nov 14;322(5904):1101-4. doi: 10.1126/science.1165218.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Experimental Immunology Branch, Center for Cancer Research, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19008446" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Bronchoalveolar Lavage Fluid/cytology/immunology
;
Carrier Proteins/*physiology
;
*Cell Adhesion
;
Endothelial Cells/*physiology
;
Intercellular Adhesion Molecule-1/metabolism
;
Leukocyte Rolling
;
Ligands
;
Lipopolysaccharides/immunology
;
Lung/blood supply/immunology
;
Lymphocyte Function-Associated Antigen-1/metabolism
;
Mice
;
Monocytes/*physiology
;
*Neutrophil Infiltration
;
Neutrophils/*physiology
;
Peritonitis/immunology
;
Pneumonia/*immunology
;
Recombinant Fusion Proteins/metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
