2000 Fiscal Year Final Research Report Summary
MOLECULAR BIOLOGICAL STUDY FOR EFFECT OF PULMONARY SURFACTANT PROTEINS ON HOST DEFENSE MECHANISM IN LUNG
| Project/Area Number |
11670585
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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 | SAPPORO MEDICAL UNIVERSITY |
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Principal Investigator |
TAKAHASHI Hiroki SCHOOL OF MEDICINE, SAPPORO MEDICAL UNIVERSITY, ASSOCIATE PROFESSOR, 医学部, 助教授 (60231396)
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| Co-Investigator(Kenkyū-buntansha) |
KUROKI Yoshio SCHOOL OF MEDICINE, SAPPORO MEDICAL UNIVERSITY, PROFESSOR, 医学部, 教授 (70161784)
ABE Shosaku SCHOOL OF MEDICINE, SAPPORO MEDICAL UNIVERSITY, PROFESSOR, 医学部, 教授 (60113510)
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| Project Period (FY) |
1999 – 2000
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| Keywords | PULMONARY SURFACTANT / SP-A / SP-D / IDIOPATHIC PULMONARY FIBROSIS / ALVEOLAR MACROPHAGE / CD14 |
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| Research Abstract |
Idiopathic pulmonary fibrosis (IPF) are often exacerbated by a trigger of respiratory infection which is the highest risk factor to threaten patients with death. We had reported that concentrations of serum surfactant protein (SP)-A and -D, collectins derived from lung, show to be low in alveolar washing fluids from patients with IPF, while high in sera from the patients when compared to healthy adults. Considering based on these results, we proposed a hypothesis that alteration in concentration of the intrapulmonary and serum collectins affects progress of IPF and prognosis.
Investigation of outcome in patients with IPF in a 3-year-observation period revealed that concentrations of serum collectins at an initial time-point of observation were significantly higher in nonsurvivors than in survivors. Experiments using an animal model of interstitial lung injury showed that concentrations of collectins decreased in lung and increased in blood, and that an leakage of the collectins from lung to bloodstream was caused by the damage of basement membrane in alveolar wall. In in vitro experiments, it was clarified SP-A possesses abilities to bind with LPS and CD14, and to modulate the cellular response by LPS on U937 cells. SP-A also inhibited TNF-∂ release stimulated by peptidoglycan (PGN), derived from Staphylococcus aureus, in alveolar macrophages and U937 cells.
The results are consistent with our hypothesis that pulmonary collectins prevent progress of inflammation and that the abnormal decrease in concentrations of intrapulmonary collections may lead to acute exacerbation of IPF.
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