Junctional adhesion molecule A expressed on human CD34+ cells promotes adhesion on vascular wall and differentiation into endothelial progenitor cells
| Autor: | Konstantinos Stellos, Harald F. Langer, Iris I. Mueller, Boris Bigalke, Dagmar Menzel, Victoria Panagiota, Andreas Bültmann, Angela Paul, Stephan Gnerlich, Tobias Geisler, Meinrad Gawaz, Elena Ninci, Tanja Schönberger, Stephan Lindemann |
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| Rok vydání: | 2010 |
| Předmět: |
Blood Platelets
Male Time Factors Recombinant Fusion Proteins Blotting Western CD34 Immunoglobulins Antigens CD34 Receptors Cell Surface CHO Cells Mice SCID Biology Transfection Muscle Smooth Vascular Mice Vasculogenesis Cricetulus Mice Inbred NOD Cricetinae Cell Adhesion Animals Humans Progenitor cell Cell adhesion Interleukin 3 Cell Proliferation Wound Healing Microscopy Video Stem Cells Soluble cell adhesion molecules Endothelial Cells Cell Differentiation Flow Cytometry Lymphocyte Function-Associated Antigen-1 Cell biology Immunoglobulin Fc Fragments Endothelial stem cell Intestines Mice Inbred C57BL Microscopy Fluorescence Reperfusion Injury Neural cell adhesion molecule Cardiology and Cardiovascular Medicine Carotid Artery Injuries Cell Adhesion Molecules Stem Cell Transplantation |
| Zdroj: | Arteriosclerosis, thrombosis, and vascular biology. 30(6) |
| ISSN: | 1524-4636 |
| Popis: | Objective— To investigate the role of junctional adhesion molecule A (JAM-A) on adhesion and differentiation of human CD34 + cells into endothelial progenitor cells. 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. Conclusion— 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. |
| Databáze: | OpenAIRE |
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