Function of Jam-B/Jam-C Interaction in Homing and Mobilization of Human and Mouse Hematopoietic Stem and Progenitor Cells

Authors

  • Marie-Laure Arcangeli,

    Corresponding author
    1. Centre de Recherche en Cancérologie de Marseille, Inserm, Marseille, France
    2. Institut Paoli-Calmettes, Marseille, France
    3. Aix-Marseille Université, Marseille, France
    4. CNRS, Marseille, France
    • Correspondence: Michel Aurrand-Lions, Ph.D., Centre de Recherche en Cancérologie de Marseille, Inserm, UMR1068, 27 Bd Leï Roure, BP30059, F-13273 Marseille Cedex 09, France. Telephone: +33(0)486977291; Fax: +33(0)486977499; e-mail: michel.aurrand-lions@inserm.fr or Marie-Laure Arcangeli, Ph.D, CEA, DSV-IRCM-SCSR-LSHL, UMR967, F-92265 Fontenay-aux roses, France. Telephone: +33(0)146547704; Fax: +33(0)146549138; e-mail: marie-laure.arcangeli@cea.fr

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  • Florence Bardin,

    1. Centre de Recherche en Cancérologie de Marseille, Inserm, Marseille, France
    2. Institut Paoli-Calmettes, Marseille, France
    3. Aix-Marseille Université, Marseille, France
    4. CNRS, Marseille, France
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  • Vincent Frontera,

    1. Centre de Recherche en Cancérologie de Marseille, Inserm, Marseille, France
    2. Institut Paoli-Calmettes, Marseille, France
    3. Aix-Marseille Université, Marseille, France
    4. CNRS, Marseille, France
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  • Ghislain Bidaut,

    1. Centre de Recherche en Cancérologie de Marseille, Inserm, Marseille, France
    2. Institut Paoli-Calmettes, Marseille, France
    3. Aix-Marseille Université, Marseille, France
    4. CNRS, Marseille, France
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  • Elodie Obrados,

    1. Centre de Recherche en Cancérologie de Marseille, Inserm, Marseille, France
    2. Institut Paoli-Calmettes, Marseille, France
    3. Aix-Marseille Université, Marseille, France
    4. CNRS, Marseille, France
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  • Ralf H. Adams,

    1. Department of Tissue Morphogenesis, Max-Planck-Institute for Molecular Biomedicine and Faculty of Medicine, University of Münster, Münster, Germany
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  • Christian Chabannon,

    1. Centre de Recherche en Cancérologie de Marseille, Inserm, Marseille, France
    2. Institut Paoli-Calmettes, Marseille, France
    3. Aix-Marseille Université, Marseille, France
    4. Inserm, CBT-510, Centre d'Investigations Cliniques en Biothérapie, Marseille, France
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  • Michel Aurrand-Lions

    Corresponding author
    1. Centre de Recherche en Cancérologie de Marseille, Inserm, Marseille, France
    2. Institut Paoli-Calmettes, Marseille, France
    3. Aix-Marseille Université, Marseille, France
    4. CNRS, Marseille, France
    • Correspondence: Michel Aurrand-Lions, Ph.D., Centre de Recherche en Cancérologie de Marseille, Inserm, UMR1068, 27 Bd Leï Roure, BP30059, F-13273 Marseille Cedex 09, France. Telephone: +33(0)486977291; Fax: +33(0)486977499; e-mail: michel.aurrand-lions@inserm.fr or Marie-Laure Arcangeli, Ph.D, CEA, DSV-IRCM-SCSR-LSHL, UMR967, F-92265 Fontenay-aux roses, France. Telephone: +33(0)146547704; Fax: +33(0)146549138; e-mail: marie-laure.arcangeli@cea.fr

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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. Stem Cells 2014;32:1043–1054

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