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.

METHODS AND 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: Konstantinos Stellos, Victoria Panagiota, Stephan Gnerlich, Oliver Borst, Boris Bigalke, Meinrad Gawaz
• Journal: Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology (Cell Physiol Biochem) Vol. 29 Issue 1-2 Pg. 153-62 ( 2012) ISSN: 1421-9778 [Electronic] Germany
• PMID: 22415084 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 S. Karger AG, Basel.

Chemical References

• Antibodies, Monoclonal
• Antigens, CD34
• Cell Adhesion Molecules
• Junctional Adhesion Molecules
• Macrophage-1 Antigen
• P-Selectin
• Peptide Fragments
• thrombin receptor peptide (42-47)

Topics

• Antibodies, Monoclonal (immunology)
• Antigens, CD34 (metabolism)
• Blood Platelets (drug effects, metabolism)
• Cell Adhesion
• Cell Adhesion Molecules (immunology, metabolism)
• Cell Differentiation
• Cells, Cultured
• Coronary Artery Disease (metabolism, pathology)
• Endothelial Cells (cytology, metabolism)
• Humans
• Junctional Adhesion Molecules
• Macrophage-1 Antigen (metabolism, physiology)
• P-Selectin (metabolism)
• Peptide Fragments (pharmacology)