TY - JOUR
T1 - Function of jam-B/Jam-C interaction in homing and mobilization of human and mouse hematopoietic stem and progenitor cells
AU - Arcangeli, Marie Laure
AU - Bardin, Florence
AU - Frontera, Vincent
AU - Bidaut, Ghislain
AU - Obrados, Elodie
AU - Adams, Ralf H.
AU - Chabannon, Christian
AU - Aurrand-Lions, Michel
PY - 2014/1/1
Y1 - 2014/1/1
N2 - 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.
AB - 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.
KW - Adhesion receptors
KW - Adult hematopoietic stem cells
KW - Hematopoietic stem cell transplantation
KW - Mobilization
KW - NOD/SCID chimeras
UR - http://www.scopus.com/inward/record.url?scp=84896356092&partnerID=8YFLogxK
U2 - 10.1002/stem.1624
DO - 10.1002/stem.1624
M3 - Article
C2 - 24357068
AN - SCOPUS:84896356092
SN - 1066-5099
VL - 32
SP - 1043
EP - 1054
JO - Stem Cells
JF - Stem Cells
IS - 4
ER -