| Project/Area Number |
07457151
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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 |
Respiratory organ internal medicine
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| Research Institution | KANAZAWA MEDICAL UNIVERSITY |
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Principal Investigator |
TAKAHASHI Keiji KANAZAWA MEDICAL UNIV., DEPT OF INTERNAL MED., PROF., 医学部, 教授 (50004685)
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| Co-Investigator(Kenkyū-buntansha) |
NAMBU Yoshihiro KANAZAWA MEDICAL UNIV., DEPT.OF INTERNAL MED., LECTURER, 医学部, 講師 (20237639)
OSANAI Kazuhiro KANAZAWA MEDICAL UNIV., DEPT.OF INTERNAL MED., LECTURER, 医学部, 講師 (70221158)
TOGA Hirohisa KANAZAWA MEDICAL UNIV., DEPT.OF INTERNAL MED., ASSO.PROF., 医学部, 助教授 (90142554)
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| Project Period (FY) |
1995 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥7,400,000 (Direct Cost: ¥7,400,000)
Fiscal Year 1997: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1996: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1995: ¥4,200,000 (Direct Cost: ¥4,200,000)
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| Keywords | Lung injury / Alveolar type II cell / Inflammatory cytokines / Interleukin-1 beta / Lung surfactant / Alveolar fluid clearance / 肺気腫 / 肺線維症 / サイトカイン / NO / アポトーシス / Matrix metallo proteinase / II型肺胞上皮細胞 / IL-1B / 肺組織障害 / 肺線維定 / サイトカイン受容体 / 活性酸素 |
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| Research Abstract |
PURPOSE : Proliferation of alveolar type II cells is critical for restoration of the integrity of alveolar injuries caused by a number of different etiologies, In this project, we aimed to investigate interactions between alveolar type II cell and inflammatory cytokines and or mediators in the lung injury. RESULTS : 1) Alveolar type II cells and inflammatory cytokines. IL-1 beta enhanced a [^3H] Thymidine incorporation dose- and time-dependently into DNA in rat alveolar type II cells. Anti-IL-1 beta antibody or IL-1 receptor antagonist partially inhibited thee effects of IL-1 beta on [^3H] Thymidine incorporation. Their combination completely inhibited the effects of IL-1 beta. In the absence of IL-1 beta, the combination inhibited the [^3H] Thymidine incorporation to a level under that in the control. These results dumonstrate that exogenous IL-1 beta stimulates DNA synthesis in alveolar type II cells and the cells also produce IL-1 beta endogenously, and suggest that the endogenous I
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L-1 beta may mediate basal DNA synthesis of alveolar type cells. Lung surfactant and lung injury. We invastigated potential interactions between exogenous surfactant (Surfactant TA) and neutrophil functions. Neutrophil alveolitis was induced in hamster lungs by the intratracheal administration of bleomycin (5mg/kg) on Day 0. Some of the animals were followed by replacement with Surfactant TA (5 and 10mg/1OOg BW) on Day 1. Alveolar cells were harvested by lung lavage on Day 2. The numbers of the neutrophils obtained from the lungs treated with bleomycin and Surfactant were unchanged, but the superoxido production from these cells was significantly decreased when compared with control animals (no Surfactant TA). From the in vitro experiments Surfactant TA was shown to inhibit adherence and superoxide production of human neutrophils. Surfactant-TA-treated neutrophils were demonstrated to have picnotic nuclei and to express Fas antigens, which were characteristic of apoptotic cells. These results suggest that exogenous Surfactant TA may play an important role not only in improving surfactant functions but in preventing neutrophils from further activation, probably through enhancing apoptosis. 3) Mechanisms of alveolar fluid clearance. Alveolar sodium enters through sodium channels on the apical membrane of alveolar type II cells and is pumped out by a Na, K-^<ATP> ase on the basolateral membrane. Water follows sodium movement primarily through transcellular aquaporin pathways. Alveolar fluid clearance increased by K^<ATP> channel opener which could effect K transport and net vectorial fluid movement across the human alveolar epithelium. Less
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