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

被引：244

作者：

Choi, Eun Young ^{[1
]}

Chavakis, Emmanouil ^{[2
]}

Czabanka, Marcus A. ^{[3
]}

Langer, Harald F. ^{[1
]}

Fraemohs, Line ^{[4
]}

Economopoulou, Matina ^{[5
]}

Kundu, Ramendra K. ^{[6
]}

Orlandi, Alessia ^{[2
]}

Zheng, Ying Yi ^{[1
]}

Prieto, DaRue A. ^{[7
]}

Ballantyne, Christie M. ^{[8
,9
]}

Constant, Stephanie L. ^{[10
]}

Aird, William C. ^{[11
]}

Papayannopoulou, Thalia ^{[12
]}

Gahmberg, Carl G. ^{[13
]}

Udey, Mark C. ^{[14
]}

Vajkoczy, Peter ^{[3
]}

Quertermous, Thomas ^{[6
]}

Dimmeler, Stefanie ^{[2
]}

Weber, Christian ^{[4
]}

Chavakis, Triantafyllos ^{[1
]}

机构：

[1] NCI, Expt Immunol Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA

[2] Univ Frankfurt, Dept Internal Med 3, Frankfurt, Germany

[3] Charite Univ Med Berlin, Dept Neurosurg, D-13353 Berlin, Germany

[4] Rhein Westfal TH Aachen, Univ Hosp, Inst Mol Cardiovasc Res, Aachen, Germany

[5] NCI, Lab Cellular Oncol, Canc Res Ctr, NIH, Bethesda, MD 20892 USA

[6] Stanford Univ, Sch Med, Div Cardiovasc Med, Palo Alto, CA 94304 USA

[7] NCI, Lab Proteom & Anal Technol, SAIC Frederick, Frederick, MD 21701 USA

[8] Baylor Coll Med, Houston, TX 77030 USA

[9] Methodist DeBakey Heart & Vasc Ctr, Ctr Cardiovasc Dis Prevent, Houston, TX 77030 USA

[10] George Washington Univ, Dept Microbiol Immunol & Trop Med, Washington, DC USA

[11] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA USA

[12] Univ Washington, Dept Med Hematol, Seattle, WA 98195 USA

[13] Univ Helsinki, Div Biochem, Fac Biosci, Helsinki, Finland

[14] NCI, Dermatol Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA

来源：

SCIENCE | 2008年 / 322卷 / 5904期

关键词：

D O I：

10.1126/science.1165218

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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- /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.

引用

页码：1101 / 1104

页数：4

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