1999 Fiscal Year Final Research Report Summary
Host defense mechanism by pulmonary surfactant proteins A and D thiir clinical application
| Project/Area Number |
10557058
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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 | 展開研究 |
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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 |
KUROKI Yoshio Sapporo Medical University, School of Medicine, Professor, 医学部, 教授 (70161784)
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| Co-Investigator(Kenkyū-buntansha) |
NAGATAM Atsuo Yamasa Corporation Diagnostic Division, Head, 診断薬部, 室長
SANO Hitomi Sapporo Medical University, School of Medicine, Research Associate, 医学部, 助手 (80295344)
SOHMA Hitoshi Sapporo Medical University, School of Medicine, Assistant Professor, 医学部, 講師 (70226702)
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| Project Period (FY) |
1998 – 1999
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| Keywords | surfactant proteins / collectins / host defense mechanism / lipopolysaccharide / CD14 / interstitial pneumonia / lung adenocarcinomas / ARDS |
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| Research Abstract |
The purpose of this study were to investigate the molecular mechanism of host defense by pulmonary surfactant proteins SP-A and SP-D and to establish the application for their clinical uses.
(1) The SP-A/MBP-A chimera in which the rat SP-A region of Thr174-Gly194 was replaced with the MBP-A region of Thr164-Asp184 lost the SP-A functions of DPPC binding, Ca2+-dependent GalCer binding and interacting with alveolar type II cells but acquired the MBP activity of binding PI. The synthetic peptide corresponding to this SP-A region was used to interact with LPS and peptideglycans.
(2) SP-A and SP-D interact with the peptide portion and the oligosaccharide moieties of CD14, respectively. SP-A and SP-D altered the interaction of CD14 with LPS.
(3) The SP-A levels but not the SP-D levels significantly decreased in BAL fluids of patients with ARDS. The patients with ARDS at risk that did not exhibit low SP-A levels did not develop ARDS.
(4) The detection of serum SP-A and SP-D reflected the small in
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terstitial pathological changes of patients with collagen vascular diseases that might be detected by chest CT but not by plain chest Xp.
(5) The large scale production system of recombinant SP-A and SP-D was established by CHO-K1 cells and pEE14 vectors using glutamine synthetase system.
(6) The contents of SP-A and SP-D increased in BAL fluids of rats with diabetes mellitus, suggesting that SP-A and SP-D function as acute phase reactants.
(7) The carboxy terminal 25 amino acids have been identified to be essential for the interactions of SP-A and SP-D with their ligands by analysis with SP-A/SP-D chimeras.
(8) The SP-A expression was examined in bone marrow of patients with primary lung adenocarcinomas. There were significant correlations between expressions of SP-A (immunostaining and mRNA) and cytokeratin. The patients with SP-A positive in bone marrow tend to show high scores of tumor fibrosis and of vessel invasion, and C-F types of Noguchi classification, suggesting the usefulness of SP-A expression to detect micrometastasis of lung adenocarcinomas. Less
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