2000 Fiscal Year Final Research Report Summary
Study on pathogenesis of idiopathic interstitial pneumonia : Analysis of Hermansky-Pudlak syndrome as a model.
| Project/Area Number |
11670184
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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 |
Human pathology
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| Research Institution | Yokohama City University |
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Principal Investigator |
NAKATANI Yukio Yokohama City University Hospital, Associate Professor, 医学部・附属病院, 助教授 (20137037)
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| Co-Investigator(Kenkyū-buntansha) |
MIYAGI Yohei Yokohama City University School of Medicine, Lecturer, 医学部, 講師 (00254194)
YAMANAKA Shoji Yokohama City University School of Medicine, Lecturer, 医学部, 講師 (80264604)
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| Project Period (FY) |
1999 – 2000
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| Keywords | Interstitial pneumonia / Hermansky-Pudlak syndrome / Type II pneumocte / ep mouse / Amiodarone |
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| Research Abstract |
1)The lung tissue of ep mice, a mouse model of Hermansky-Pudlak syndrome, was studied light microscopically and ultrastructurally. Type II pneumocytes of the ep mouse lung showed foamy swelling/degeneration after the age of 4 weeks old at the light microscopic level. Ultrastructurally, giant lamellar bodies appeared within the type II pneumocytes at the age of 8 days, and thereafter increased in size and number. This change (GLBD) was almost identical to that of the lung affected by interstitial pneumonia in patients with Hermansky-Pudlak syndrome (HPSIP), suggesting the ep mouse being a good mouse model for clarifying the pathogenesis of HPSIP.Alveolitis, however, has not been observed in the ep mouse lung so far, and further observation is being conducted.
2)The lung tissue of ep mice with oral administration of amiodarone at the dose of 400 mg/kg/day for 6 weeks showed mild alveolitis with mononuclear cell infiltration of the alveolar septa.
3)Rabbit polyclonal antibody was raised against a polypeptide corresponding to the 23 amino acid residues encoded at the carboxyl terminal portion of 1.5kb cDNA from the HPS1 gene. This antibody (HPS1/ep antibody) and the mouse monoclonal antibody against the HPS1 protein (clone : hHPS5) supplied by Dr.Spritz were used to to localize the HPS protein in various tissues immunohistochemically. Alveoalr macrophages, renal tubular epithelium and melanoma cells showespecially intense staining in the cytoplasm. HPS1/ep antibody also stained type II pneumocytes. Lungs affected by HPSIP showed heterogeneity in the staining of type II pneumocytes according to the cases. The lungs of ep mice showed intense staining of the marginal contour of cytolasmic vacuoles in the type II pneumocytes, suggesting that dysfunction of the defective HPS protein may be the cause of GLBD.
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