LFA-1 and VLA-4 involved in human high proliferative potentialendothelial progenitor cells homing to ischemic tissue

Huaxin Duan; Lamei Cheng; Xuan Sun; Yonggang Wu; Liangshan Hu; Jian Wang; Huiping Zhao; Guangxiu Lu

doi:10.1160/TH06-04-0199

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2006; 96(06): 807-815
DOI: 10.1160/TH06-04-0199

Endothelium and Vascular Development

Schattauer GmbH

LFA-1 and VLA-4 involved in human high proliferative potentialendothelial progenitor cells homing to ischemic tissue

Authors

Huaxin Duan

¹National Center of Human Stem Cell Research and Engineering, Institute of Human Reproduction and Stem Cell Engineering, Central South University, Changsha, China
Lamei Cheng

¹National Center of Human Stem Cell Research and Engineering, Institute of Human Reproduction and Stem Cell Engineering, Central South University, Changsha, China
Xuan Sun

¹National Center of Human Stem Cell Research and Engineering, Institute of Human Reproduction and Stem Cell Engineering, Central South University, Changsha, China
Yonggang Wu

¹National Center of Human Stem Cell Research and Engineering, Institute of Human Reproduction and Stem Cell Engineering, Central South University, Changsha, China
Liangshan Hu

¹National Center of Human Stem Cell Research and Engineering, Institute of Human Reproduction and Stem Cell Engineering, Central South University, Changsha, China
Jian Wang

¹National Center of Human Stem Cell Research and Engineering, Institute of Human Reproduction and Stem Cell Engineering, Central South University, Changsha, China
Huiping Zhao

¹National Center of Human Stem Cell Research and Engineering, Institute of Human Reproduction and Stem Cell Engineering, Central South University, Changsha, China
Guangxiu Lu

¹National Center of Human Stem Cell Research and Engineering, Institute of Human Reproduction and Stem Cell Engineering, Central South University, Changsha, China

Abstract

Summary

Cumulative evidences have revealed that endothelial progenitor cell (EPC) transplantation can promote the neovascularization in ischemic tissue, but the mechanism of EPCs homing to the site of ischemia is poorly understood. In this study, to investigate the mechanism of human umbilical cord blood-derived high proliferative potential-endothelial progenitor cells (HPP-EPCs) homing to ischemic tissue we evaluated the expression of lymphocyte function-associated antigen-1 (LFA-1, or CD11a/CD18) and very late antigen-4 (VLA-4, or CD49d/CD29) in EPCs and the changes of expression level of their ligands, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), in ischemic tissue and performed the adhesion and migration assays to analyze the interaction between the receptors and ligands. Furthermore, we studied the roles of LFA-1 and VLA-4 in EPC homing in an ischemic model of mice. The results show that LFA-1 andVLA-4 were expressed in HPPEPCs and ICAM-1 and VCAM-1 were expressed in vessel endothelium in ischemic tissues. The pre-incubation of HPP-EPCs with neutralizing antibodies against CD11a or CD49d reduced adhesion and migration of HPP-EPCs in vitro and reduced recovery of hind-limb blood flow, capillary density and incorporation of HPP-EPC into ischemic tissues in vivo. Furthermore, the pre-incubation of HPP-EPCs with the combination of CD11a and CD49d antibodies led to synergistically negative effects on adhesion and transmigration of HPP-EPCs in vitro, and on the homing of HPP-EPCs to ischemic tissue and on neovascularization capacity in vivo. These results indicate that LFA-1 andVLA-4 are involved in HPP-EPC homing to ischemic tissues.

Keywords

Endothelial progenitor cells - homing - ischemia - adhesion molecules

Full Text

References

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