title: Expression of junctional adhesion molecule-C on the surface of platelets supports adhesion, but not differentiation, of human CD34 cells in vitro.
abstract: BACKGROUND
  CD34(+) progenitor cells play an important role in haematopoiesis and vascular homeostasis. The aim of the present study was to investigate the role of platelet-derived junctional adhesion molecule-C (JAM-C) in adhesion and differentiation of human CD34(+) cells in vitro, as well as its association with platelet-derived P-selectin in patients with coronary artery disease.
  
  
  RESULTS
  Using flow cytometry we observed that JAM-C expression on the surface of washed platelets is increased after activation with thrombin receptor activating peptide-6 in vitro and correlated with platelet-derived P-selectin expression in patients with coronary artery disease (r=0.326, P=0.007). The role of JAM-C and its counter receptor Mac-1 in adhesion of human CD34(+) cells over immobilized platelets was investigated by using a neutralizing soluble protein (sJAM-C-Fc) and a monoclonal antibody against JAM-C or integrin Mac-1 (CD11b/CD18). Treatment with soluble JAM-C-Fc or anti-JAM-C or anti-Mac-1, but not with control-Fc or IgG1, resulted in a significantly decreased adhesion of human CD34(+) cells to platelets under static conditions (P<0.05). In order to validate our findings under high shear stress we performed flow chamber experiments. In a similar manner, inhibiting JAM-C interaction with Mac-1 resulted in a significantly decreased adhesion of CD34(+) cells over immobilized platelets under high shear stress (P<0.05). Colony forming unit assays and coculture assays revealed that inhibition of JAM-C/Mac-1 axis did not influence the platelet-mediated differentiation of CD34(+) cells to endothelial cells or to macrophages/foam cells.
  
  
  CONCLUSIONS
  Taken together a platelet-derived JAM-C supports CD34(+) cell adhesion, a mechanism potentially involved in homing as well as domiciliation of human CD34(+) cells.
authors.affiliation: Medizinische Klinik III, Kardiologie und Kreislauferkrankungen, Eberhard-Karls-Universität Tübingen, Tübingen, Germany. konstantinos.stellos@gmail.com
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Stellos
authors.forename: Victoria
authors.initials: V
authors.lastname: Panagiota
authors.forename: Stephan
authors.initials: S
authors.lastname: Gnerlich
authors.forename: Oliver
authors.initials: O
authors.lastname: Borst
authors.forename: Boris
authors.initials: B
authors.lastname: Bigalke
authors.forename: Meinrad
authors.initials: M
authors.lastname: Gawaz
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology; D018952:Antigens, CD34 / Q000378:metabolism*; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000276:immunology / Q000378:metabolism*; D002454:Cell Differentiation; D002478:Cells, Cultured; D003324:Coronary Artery Disease / Q000378:metabolism / Q000473:pathology; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D062726:Junctional Adhesion Molecules; D016177:Macrophage-1 Antigen / Q000378:metabolism / Q000502:physiology; D019007:P-Selectin / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology
chemical_list: D000911:Antibodies, Monoclonal; D018952:Antigens, CD34; D015815:Cell Adhesion Molecules; D062726:Junctional Adhesion Molecules; D016177:Macrophage-1 Antigen; D019007:P-Selectin; D010446:Peptide Fragments; C082835:thrombin receptor peptide (42-47)