Role of CXC chemokines in pulmonary alveolar injury under mechanical stress
| Project/Area Number |
13670621
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 UNIVERCITY |
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Principal Investigator |
TOGA Hirohisa KANAZAWA MEDICAL UNIVERCITY, Kanazawa Medical University Department of Medicine, Associate Professor (90142554)
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| Co-Investigator(Kenkyū-buntansha) |
KANAZAWA Keiji Kanazawa Medical University, Department of Medicine, Professor (50004685)
TOBE Takeyasu Kanazawa Medical University, Department of Medicine, Assistant Professor (90329409)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2002: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | ventilator-induced lung injury / CXC chemokine / cytokine-induced neutrophil chemoattractant-1 / broncho-alveolar lavage / neutralizing antibody / neutrophil / alveolar type II cells / pressure load / VILI / CINC-1 / RT-PCR |
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| Research Abstract |
1. Rat ventilator-induced lung injury (VILI) model
Rats were mechanically ventilated with a tidal volume (TV) of either 10ml/kg BW (low TV) or 30ml/kg BW (high TV) for 3 hours. Congestion, alveolar bleeding and neutrophil infiltration were observed in rats of high TV, indicating that VILI was induced in this TV. Among the group of CXC chemokines, cytokine-induced neutrophil chemoattractant-1 (CINC-1) concentration in broncho-alveolar lavage fluid (BALF) was significantly higher in the high TV group than the low TV group (p<0.05). Immunohistochemistry showed that CINC-1 was expressed in peripheral airways and alveolar epithelial cells. Expression of CINC-1 mRNA was also augmented in the high TV group.
2. Effects of anti-CINC-1 antibodies on VILI
Pre-treatment with a rabbit anti-rat CINC-1 polyclonal antibody at concentrations of 50, 100, 200 and 500μg/body significantly inhibited VILI in a dose-dependent manner ; histological findings improved, BALF protein concentration reduced and BALF neutrophil count decreased. Mortality rate was reduced. The increase in BALF CINC-1 concentration in VILI was also inhibited, confirming the neutralizing effect of the antibody.
3. CINC-1 production in rat alveolar type II cells under mechanical stress
Pressure load of 50cmH_2O, 15 times/min for 3 hours on isolated type II cells significantly increased CINC-1 concentration in the culture medium. Pretreatment with steroid reduced CINC-1 production, but the pressure load on steroid treated cells again induced an increase in CINC-1 concentration. Type II cells produced CINC-1 in response to mechanical stress such as pressure.
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Report
(3 results)
Research Products
(25 results)
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[Journal Article] Mechanical stress on type II alveolar epithelial cells and production of CXC chemokines.2003
Author(s)
Toga H, Tsuchihara K, Hida M, Nakamura K, Tsuchihara C, Tobe T, Iguchi M, Ishigaki M, Nambu Y, Osanai K, Sakuma T, Takahashi K.
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Journal Title
J Jpn Med Soc Biol Interface 34
Pages: 77-80
NAID
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Apoptosis of alveolar type II cells in acute respiratory distress syndrome.2001
Author(s)
Toga H, Kasakura H, Tobe T, Ueda Y, Yang G, Okada T, Nambu Y, Osanai K, Sakuma T, Takahashi K, Ohya N.
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Journal Title
J Jpn Med Soc Biol Interface 32
Pages: 24-25
Description
「研究成果報告書概要(欧文)」より
Related Report
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