title: Function of Jam-B/Jam-C interaction in homing and mobilization of human and mouse hematopoietic stem and progenitor cells.
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.
authors.affiliation: 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.
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Arcangeli
authors.forename: Florence
authors.initials: F
authors.lastname: Bardin
authors.forename: Vincent
authors.initials: V
authors.lastname: Frontera
authors.forename: Ghislain
authors.initials: G
authors.lastname: Bidaut
authors.forename: Elodie
authors.initials: E
authors.lastname: Obrados
authors.forename: Ralf H
authors.initials: RH
authors.lastname: Adams
authors.forename: Christian
authors.initials: C
authors.lastname: Chabannon
authors.forename: Michel
authors.initials: M
authors.lastname: Aurrand-Lions
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002450:Cell Communication / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D005260:Female; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods*; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D062765:Junctional Adhesion Molecule B
chemical_list: D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; C411887:JAM2 protein, human; D062765:Junctional Adhesion Molecule B; C448000:JAM3 protein, human; C498781:Jam2 protein, mouse; C486723:Jam3 protein, mouse
keywords: Adhesion receptors; Adult hematopoietic stem cells; Hematopoietic stem cell transplantation; Mobilization; NOD/SCID chimeras