ROLE OF APOPTOSIS IN EMPHYSEMA

• Project/Area Number: 14570539
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Chiba University
• Principal Investigator: KASAHARA Yasunori Chiba University, Graduate School of Medicine, Assistant, 大学院・医学研究院, 助手 (60343092)
• Co-Investigator(Kenkyū-buntansha): KUROSU Katsushi Chiba University, Graduate School of Medicine, Assistant, 大学院・医学研究院, 助手 (20291106) ; TATSUMI Koichiro Chiba University, Graduate School of Medicine, Associate Professor, 大学院・医学研究院, 助教授 (10207061)
• Project Period (FY): 2002 – 2003
• Project Status: Completed (Fiscal Year 2003)
• Budget Amount: ¥3,600,000 (Direct Cost: ¥3,600,000); Fiscal Year 2003: ¥1,300,000 (Direct Cost: ¥1,300,000); Fiscal Year 2002: ¥2,300,000 (Direct Cost: ¥2,300,000)
• Keywords: COPD / emphysema / smoking / VEGF / apoptosis / mouse / caspase-3 / endothelial cell / caspase-3

Research Abstract

Introduction : We have postulated that cigarette smoking induced emphysema may occur due to a failure of the cellular and molecular maintenance program of the lung. There is a loss of alveolar structures and almost avascular in emphysema. This observation suggests to us that the disappearance of lung tissue in emphysema may involve in the progressive loss of capillary endothelial cells. Cigarette smoking is a major risk factor of endothelial dysfunction. We hypothesize that the level of endotheliqirogenitor cells (EPC) may contribute the progressive loss of capillary endothelial cells in emphysema.
Methods : C57BL/6J mice were exposed to cigarette smoking 5 days/week, 20 cigarettes/day, for 2 weeks. Peak carboxyhemoglobin blood concentration was abut 10%. Mononuclear cells were isolated from bone marrow and peripheral blood cells by density gradient centrifugation. We quantified the number of KDR/S_<Ga>(Stem cell antigen-l) double positive cells using 2-color flow cytometric analyses.
Re sults : The mean linear intercept, as a measure of interalveolar wall distance, was significantly. greater in smoking mice lungs when compared with controlmice lungs (53.8±5.9 vs. 40.7±2.7, P < 0.01). VEGF protein measured in whole lung homogenatesby ELISA was significantly (P < 0.01) decreased smoking mice lungs (150.9±10.6 pg/mg) when compared with lungs of normals(196.4±6.5 pg/mg). However, the caspase-3 like activity was not significantly different between smoking and control mice (20.4±8.9 vs. 15.4±11.7 pNA pM),there are some TUNEL-positive cells in the lungs of cigarettes smoke exposure mice KDR/Sca-1 double positive cells in the peripheral blood of smoking mice were not significantly differed (0.52±0.20% vs. 0.94±0.69%). However, the smoking mouse had significantly increased the number of EPCs in the bone marrow (0.48±0.16 vs. 0.84±0.46%, P<0.02)
Conclusions : Lung cell apoptosis following decreased expression of lung VEGF may be important role in the pathogenesis of emphysema. We conclude that bone marrow derived endothelial progenitor cells are increased in the cigarette smoke exposure mice. Endothelial progenitor cells may be important in compensation for endothelial dysfunction of smoking mouse.

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