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Junctional adhesion molecule A expressed on human CD34+ cells promotes adhesion on vascular wall and differentiation into endothelial progenitor cells.
- Source :
-
Arteriosclerosis, thrombosis, and vascular biology [Arterioscler Thromb Vasc Biol] 2010 Jun; Vol. 30 (6), pp. 1127-36. Date of Electronic Publication: 2010 Apr 08. - Publication Year :
- 2010
-
Abstract
- Objective: To investigate the role of junctional adhesion molecule A (JAM-A) on adhesion and differentiation of human CD34(+) cells into endothelial progenitor cells.<br />Methods and Results: Tissue healing and vascular regeneration is a multistep process requiring firm adhesion of circulating progenitor cells to the vascular wall and their further differentiation into endothelial cells. The role of JAM-A in platelet-mediated adhesion of progenitor cells was investigated by adhesion assays in vitro and with the help of intravital fluorescence microscopy in mice. Preincubation of human CD34(+) progenitor cells with soluble JAM-A-Fc (sJAM-A-Fc) resulted in significantly decreased adhesion over immobilized platelets or inflammatory endothelium under high shear stress in vitro and after carotid ligation in vivo or ischemia/reperfusion injury in the microcirculation of mice. Human CD34(+) cells express JAM-A, as defined by flow cytometry and Western blot analysis. JAM-A mediates differentiation of CD34(+) cells to endothelial progenitor cells and facilitates CD34(+) cell-induced reendothelialization in vitro. Pretreatment of human CD34(+) cells with sJAM-A-Fc resulted in increased neointima formation 3 weeks after endothelial denudation in the carotid arteries of nonobese diabetic/severe combined immunodeficient mice.<br />Conclusions: These results indicate that the expression of JAM-A on CD34(+) cells mediates adhesion to the vascular wall after injury and differentiation into endothelial progenitor cells, a mechanism potentially involved in vascular regeneration. Human CD34(+) cells express JAM-A, mediating their interaction with platelets and endothelial cells. Specifically, JAM-A expressed on human CD34(+) progenitor cells regulates their adhesion over immobilized platelets or inflammatory endothelium under high shear stress in vitro and after carotid ligation in vivo or ischemia/reperfusion injury in the microcirculation of mice. Moreover, it mediates differentiation of CD34(+) cells to endothelial progenitor cells and facilitates reendothelialization.
- Subjects :
- Animals
Blood Platelets metabolism
Blotting, Western
CHO Cells
Carotid Artery Injuries blood
Carotid Artery Injuries immunology
Carotid Artery Injuries pathology
Carotid Artery Injuries physiopathology
Cell Adhesion Molecules genetics
Cell Proliferation
Cricetinae
Cricetulus
Endothelial Cells immunology
Endothelial Cells transplantation
Flow Cytometry
Humans
Immunoglobulin Fc Fragments metabolism
Immunoglobulins genetics
Lymphocyte Function-Associated Antigen-1 metabolism
Male
Mice
Mice, Inbred C57BL
Mice, Inbred NOD
Mice, SCID
Microscopy, Fluorescence
Microscopy, Video
Muscle, Smooth, Vascular metabolism
Muscle, Smooth, Vascular pathology
Receptors, Cell Surface
Recombinant Fusion Proteins metabolism
Reperfusion Injury blood
Reperfusion Injury immunology
Reperfusion Injury pathology
Reperfusion Injury physiopathology
Stem Cell Transplantation
Stem Cells immunology
Time Factors
Transfection
Wound Healing
Antigens, CD34 analysis
Carotid Artery Injuries metabolism
Cell Adhesion
Cell Adhesion Molecules metabolism
Cell Differentiation
Endothelial Cells metabolism
Immunoglobulins metabolism
Intestines blood supply
Reperfusion Injury metabolism
Stem Cells metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1524-4636
- Volume :
- 30
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Arteriosclerosis, thrombosis, and vascular biology
- Publication Type :
- Academic Journal
- Accession number :
- 20378847
- Full Text :
- https://doi.org/10.1161/ATVBAHA.110.204370