Role of MAdCAM-1 and its ligand on the homing of transplanted hematopoietic cells in irradiated mice.
We examined the expression of VCAM-1 and MAdCAM-1 after bone marrow transplantation (BMT). We also examined the influence of alpha(4)beta(7) integrin blockade on the homing of cells to the bone marrow and spleen. The expression of VCAM-1 and MAdCAM-1 by endothelial cells in the spleen and bone marrow was examined by immunoelectron microscopy using colloidal gold and was analyzed semiquantitatively. To examine the role of alpha(4)beta(7) integrin in donor cells, a homing assay was conducted following alpha(4)beta(7) integrin blockade in bone marrow-derived hematopoietic cells or spleen colony cells. Immediately after BMT, the expression of VCAM-1 and MAdCAM1 markedly decreased, but expression recovered significantly between 12 and 24 h after BMT. VCAM-1 recovered more acutely than MAdCAM-1 from 12 h onward. In the group transplanted with anti-alpha(4)beta(7) integrin antibody-treated bone marrow cells, the numbers of homing cells in the spleen and bone marrow were significantly decreased in an antibody dose-dependent manner. However, the number of homing cells was not different in either the spleen or bone marrow between anti-alpha(4)beta(7) integrin antibody treated and untreated spleen colony cells. It has been reported that alpha(4)beta(1) integrin and its receptor VCAM-1 play major roles in the homing of hematopoietic cells to bone marrow. Our study indicates the importance of MAdCAM-1 and its ligand, alpha(4)beta(7) integrin, in the homing of bone marrow-derived hematopoietic cells, but not spleen colony-derived cells, to both the spleen and bone marrow.
Tada
Tatsuya
T
Laboratory of Animal Morphology and Function, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Japan.
Inoue
Naoko
N
Widayati
Diah Tri
DT
Fukuta
Katsuhiro
K
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D015815:Cell Adhesion Molecules; D018380:Hematopoietic Stem Cell Transplantation; D007136:Immunoglobulins / Q000502:physiology*; D039041:Integrin alpha4beta1 / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009088:Mucoproteins / Q000502:physiology*; D013154:Spleen / Q000166:cytology; D019010:Vascular Cell Adhesion Molecule-1 / Q000502:physiology*
D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; D039041:Integrin alpha4beta1; C504265:MADCAM1 protein, human; D009088:Mucoproteins; D019010:Vascular Cell Adhesion Molecule-1