Junctional adhesion molecule A expressed on human CD34+ cells promotes adhesion on vascular wall and differentiation into endothelial progenitor cells.
OBJECTIVE
To investigate the role of junctional adhesion molecule A (JAM-A) on adhesion and differentiation of human CD34(+) cells into endothelial progenitor cells.


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.


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.
Stellos
Konstantinos
K
Medizinische Klinik III, Kardiologie und Kreislauferkrankungen, Eberhard Karls-Universität Tübingen, Otfried-Müller Strasse 10, 72076 Tübingen, Germany. konstantinos.stellos@med.uni-tuebingen.de
Langer
Harald
H
Gnerlich
Stephan
S
Panagiota
Victoria
V
Paul
Angela
A
Schönberger
Tanja
T
Ninci
Elena
E
Menzel
Dagmar
D
Mueller
Iris
I
Bigalke
Boris
B
Geisler
Tobias
T
Bültmann
Andreas
A
Lindemann
Stephan
S
Gawaz
Meinrad
M
D000818:Animals; D018952:Antigens, CD34 / Q000032:analysis*; D001792:Blood Platelets / Q000378:metabolism; D015153:Blotting, Western; D016466:CHO Cells; D020212:Carotid Artery Injuries / Q000097:blood / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D049109:Cell Proliferation; D006224:Cricetinae; D003412:Cricetulus; D042783:Endothelial Cells / Q000276:immunology / Q000378:metabolism* / Q000637:transplantation; D005434:Flow Cytometry; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000378:metabolism; D007136:Immunoglobulins / Q000235:genetics / Q000378:metabolism*; D007422:Intestines / Q000098:blood supply*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008856:Microscopy, Fluorescence; D018715:Microscopy, Video; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015427:Reperfusion Injury / Q000097:blood / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000276:immunology / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection; D014945:Wound Healing
D018952:Antigens, CD34; D015815:Cell Adhesion Molecules; C407243:F11R protein, human; D007141:Immunoglobulin Fc Fragments; D007136:Immunoglobulins; D016169:Lymphocyte Function-Associated Antigen-1; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins