| Co-Investigator(Kenkyū-buntansha) |
MARUYAMA Junko Mie University, Graduate school of Medicine, Lecturer, 大学院・医学系研究科, 講師 (50263017)
DEGUCHI Takao Mie University, University Hospital, Assistant professor, 医学部附属病院, 助手 (70345990)
MARUYAMA Kazuo Mie University, Graduate school of Medicine, Professor, 大学院・医学系研究科, 教授 (20181828)
KOMADA Yoshihiro Mie University, Graduate school of Medicine, Professor, 大学院・医学系研究科, 教授 (80186791)
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| Budget Amount *help |
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2005: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2004: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Research Abstract |
We investigated whether BM-derived cells are incorporated into pulmonary vascular lesions in mice exposed to chronic hypoxia, by using bone marrow transplantation (BMT) model. Wild-type mice were lethally irradiated and transplanted with BM cells (2x 106) from littermates expressing enhanced green fluorescent protein (eGFP)(n=41). Six weeks after BMT, these animals were sacrificed after exposed to hypobaric hypoxia (380mmHg) for 10 or 21 days, or kept in ambient air. To evaluate the incorporation of BM-derived cells into the pulmonary vasculature, tissue sections were immunostained with cell-specific (CD31, α-actin, vimentin, CD45, MOMA-2) antibodies or anti-eGFP, and were analyzed using laser scanning confocal microscopy or light microscopy. Hypoxic exposure for 10 or 21 days increased right ventricle (RV) /body weight, RV/ left ventricle (LV) +septum (S) ratio, and the percentage of muscularized vessels among small pulmonary vessels (vs controls, p<0.05, respectively). CD31 (+)/eGFP (+) BM-derived endothelial cells were observed in capillaries, and small-and medium-sized pulmonary vessels in hypoxic mice, but not in normoxic mice. Vimentin (+)/CD31 (-)/eGFP (+) BM-derived fibroblasts and CD45 (+)/MOMA2(+)/eGFP (+) BM-derived macrophages were found in the adventitia around these pulmonary vessels in hypoxic mice, but not or rarely in normoxic mice, respectively. α-actin (+)/eGFP (+) BM-derived smooth muscle cells were not found in any sections investigated. BM-derived endothelial cells and fibroblasts, as well as macrophages, preferentially reside in pulmonary vascular lesions in mice exposed to chronic hypoxia, not in ones kept in ambient air. These findings suggest that BM-derived cells may positively and/or negatively regulate the development of pulmonary vascular diseases in mice exposed to chronic hypoxia.
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