| Project/Area Number |
13670621
|
|---|
| 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 | KANAZAWA MEDICAL UNIVERCITY |
|---|
Principal Investigator |
TOGA Hirohisa KANAZAWA MEDICAL UNIVERCITY, Kanazawa Medical University Department of Medicine, Associate Professor (90142554)
|
|---|
| 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)
|
|---|
| Project Period (FY) |
2001 – 2002
|
| Project Status |
Completed (Fiscal Year 2002)
|
| Budget Amount *help |
¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2002: ¥1,200,000 (Direct Cost: ¥1,200,000)
|
|---|
| 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 |
|---|
| 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.
|
