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

Thromb Haemost. 2006 Dec;96(6):807-15.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies
  • Antigens, CD / metabolism
  • Bone Marrow Cells / immunology
  • CD11a Antigen / immunology
  • Capillaries / cytology
  • Capillaries / immunology
  • Cell Adhesion
  • Cell Adhesion Molecules / metabolism
  • Cell Line
  • Cell Movement*
  • Cell Proliferation*
  • Disease Models, Animal
  • Endothelial Cells / immunology*
  • Endothelial Cells / physiology
  • Endothelial Cells / transplantation
  • Female
  • Humans
  • Integrin alpha4 / immunology
  • Integrin alpha4beta1 / analysis*
  • Intercellular Adhesion Molecule-1 / metabolism
  • Ischemia / immunology*
  • Ischemia / physiopathology
  • Ischemia / surgery
  • Lymphocyte Function-Associated Antigen-1 / analysis*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Muscle, Skeletal / blood supply*
  • RNA, Messenger / metabolism
  • Regional Blood Flow
  • Stem Cell Transplantation
  • Stem Cells / immunology*
  • Stem Cells / physiology
  • Time Factors
  • Vascular Cell Adhesion Molecule-1 / metabolism


  • Antibodies
  • Antigens, CD
  • CD11a Antigen
  • Cell Adhesion Molecules
  • ICAM-2 protein, mouse
  • Integrin alpha4beta1
  • Lymphocyte Function-Associated Antigen-1
  • RNA, Messenger
  • Vascular Cell Adhesion Molecule-1
  • Intercellular Adhesion Molecule-1
  • Integrin alpha4