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Stem Cells. 2014 Apr;32(4):1043-54. doi: 10.1002/stem.1624.

Function of Jam-B/Jam-C interaction in homing and mobilization of human and mouse hematopoietic stem and progenitor cells.

Author information

1
Centre de Recherche en Cancérologie de Marseille, Inserm, UMR1068, Marseille, France; Institut Paoli-Calmettes, Marseille, France; Aix-Marseille Université, Marseille, France; CNRS, UMR7258, Marseille, France.

Abstract

The junctional adhesion molecules Jam-b and Jam-c interact together at interendothelial junctions and have been involved in the regulation of immune response, inflammation, and leukocyte migration. More recently, Jam-c has been found to be expressed by hematopoietic stem and progenitor cells (HSPC) in mouse. Conversely, we have reported that Jam-b is present on bone marrow stromal cells and that Jam-b-deficient mice have defects in the regulation of hematopoietic stem cell pool. In this study, we have addressed whether interaction between Jam-b and Jam-c participates to HSPC mobilization or hematopoietic reconstitution after irradiation. We show that a blocking monoclonal antibody directed against Jam-c inhibits hematopoietic reconstitution, progenitor homing to the bone marrow, and induces HSPC mobilization in a Jam-b dependent manner. In the latter setting, antibody treatment over a period of 3 days does not alter hematopoietic differentiation nor induce leukocytosis. Results are translated to human hematopoietic system in which a functional adhesive interaction between JAM-B and JAM-C is found between human HSPC and mesenchymal stem cells. Such an interaction does not occur between HSPC and human endothelial cells or osteoblasts. It is further shown that anti-JAM-C blocking antibody interferes with CD34(+) hematopoietic progenitor homing in mouse bone marrow suggesting that monoclonal antibodies inhibiting JAM-B/JAM-C interaction may represent valuable therapeutic tools to improve stem cell mobilization protocols.

KEYWORDS:

Adhesion receptors; Adult hematopoietic stem cells; Hematopoietic stem cell transplantation; Mobilization; NOD/SCID chimeras

PMID:
24357068
DOI:
10.1002/stem.1624
[Indexed for MEDLINE]
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