| Project/Area Number |
10470268
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| Research Category |
Grant-in-Aid for Scientific Research (B).
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Thoracic surgery
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| Research Institution | TOHOKU UNIVERSITY |
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Principal Investigator |
TANITA Tatsuo TOHOKU UNIVERSITY, Institute of Development, Aging, and Cancer, ASSOSLATE PROFESSOR, 加齢医学研究所, 助教授 (20217144)
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| Co-Investigator(Kenkyū-buntansha) |
SAGAWA Motoyasu TOHOKU UNIVERSITY, Hospital, ASSISTANT PROFESSOR, 医学部・附属病院, 講師 (70292274)
SATO Masami TOHOKU UNIVERSITY, Hospital, ASSISTANT PROFESSOR, 医学部・附属病院, 助手 (30250830)
KONDO Takashi TOHOKU UNIVERSITY, Institute of Development, Aging, and Cancer, PROFESSOR, 加齢医学研究所, 教授 (10195901)
藤村 重文 東北大学, 加齢医学研究所, 教授 (40006078)
小野 貞文 東北大学, 加齢医学研究所, 助手 (80250827)
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| Project Period (FY) |
1998 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥13,300,000 (Direct Cost: ¥13,300,000)
Fiscal Year 2000: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1999: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1998: ¥10,900,000 (Direct Cost: ¥10,900,000)
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| Keywords | LUNG TRANSPLANTATION / LUNG INJURY / ACTIVATED NEUTROPHILS / Intracellul signal transduction / protein kinase C / vascular endothelial cells. / transendothelial electrical resistance / actin / 内皮細胞 / 接着分子 / 細胞骨格 / シグナル伝達回路 / ICAM-1 / PECAM / シグナル伝達経路 |
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| Research Abstract |
We showed that neutrophils-induced lung injury was induced by reactive oxygen species generated via xanthine oxidase (XO) following adhesion of neutrophils on the endothelial cells. Usually, XO does not exist in the neutrophils but endothelial cells. Therefore we speculate if this kind of lung injury is induced by activation of endothelial cells themselves. In the experiments of isolated perfused rat lungs, whether intracellular signal transduction systems were involved in the injury of the pulmonary vascular endothelial cells caused by activated neutrophils, we investigated using a protein kinase C antagonist. We showed that PKC antagonist ameliorated the pulmonary vascular injury caused by activated neutrophils in a dose dependent manner. Moreover, we showed that the pulmonary vascular permeability was increased by a PKC agonist without neutrophils. On the other hand, in cell culture models, it was impossible to measure protein permeability for cell culture sheets, we measured trans-
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endothelial electrical resistance (TER) across the cultured pulmonary vascular endothelial cell sheets. We continuously measured TER of the cultured cell sheets from rat pulmonary vascular endothelial cells when they were confluent and the tested the several kinds of agonists and antagonists to the cultured cell sheets. The TERs of the cultured cell sheets were decreased by PKC agonists by dose dependent manner, meanwhile DMSO, a vehicle of PKC agonist, failed. These findings supported the results from the experiment of isolated rat lungs. We also stained actin fibers in the pulmonary vascular endothelial cells. Actin fibers existed at the peripheral area of the cytosol without any stimulations, however, they were depolymerized and moved around nucleus by PKC agonist. These findings suggest that the pulmonary vascular endothelial cells were changed their morphology by depolymerizing actin fibers by PKC when they were activated by some stimulations, and finally pulmonary microvascular permeability was increased. Less
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