Del-1, an endogenous leukocyte-endothelial adhesion inhibitor, limits inflammatory cell recruitment (Science, 2008, 322:1101-1104)

報告日期: 2009/04/07
報告時間: 16:00/16:50
報告學生: 林韋伶(英文報告)
講評老師: 謝奇璋
附件下載:

http://basicmed.med.ncku.edu.tw/admin/up_img/980407-2.pdf

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

Eun Young Choi, et al.

Science 322, 1101-1104 (2008)

 

Speaker: 林韋伶

Commentator: 謝奇璋老師

Time: 2009/04/07 PM 16:00

Place: Room 602

 

Abstract

Developmental endothelial locus-1 (Del-1) is an extracellular matrix protein secreted by endothelial cells during embryonic development and regulates vascular morphogenesis and remodeling. Del-1 also stimulates angiogenesis in ischemic tissue. Leukocyte recruitment is a cascade of adhesive events to response to inflammation. However, the role of Del-1 in leukocyte adhesion is still unknown. Therefore, in this paper, the authors considered whether endothelially derived Del-1 participates in leukocyte-endothelial interactions. First, the results showed leukocytes bound to immobilized Del-1 via lymphocyte function associated antigen 1 (LFA-1, also known as αLβ2 and CD11a/CD18). Nevertheless, endothelial Del-1 deficiency increased leukocyte adhesion in vitro. Next, the authors found that the anti-adhesive effect of Del-1 was caused by interfering with the interaction between LFA-1 and intercellular adhesion molecule - 1 (ICAM-1). Also, the presence of Del-1 inhibited leukocyte firm adhesion under physiologic flow condition. In vivo, Del-1 knock-out mice had significant higher leukocyte accumulation and slower rolling velocity in inflammation and the effects was reversed by Del-1-Fc treatment or in Del-1/LFA-1 double knock-out mice. Besides, the expression of Del-1 mRNA in mouse lung was decreased after LPS administration. Thus, Del-1 acted as an endogenous anti-adhesion molecule through inhibiting LFA-1-dependent leukocyte-endothelial interaction. It is probably that Del-1 will be a therapeutic agent for anti-inflammation.

 

Reference

1.  C. Hidai et al., Cloning and characterization of developmental endothelial locus-1: An embryonic endothelial cell protein that binds the αvβ3 integrin receptor. Genes Dev. 12, 21 (1998).

2.  H. K. Ho et al., Developmental Endothelial Locus-1 (Del-1), a Novel Angiogenic Protein Its Role in Ischemia. Circulation 109, 1314 (2004).