2001 Fiscal Year Final Research Report Summary
Clinical application for pathophysiological analysis, diagnosis and treatment of lung diseases by genes and their products expressed in alveolar type II cells.
| Project/Area Number |
12557057
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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) |
MURAKAMI Seiji Sapporo Medical University School of medicine, Research Associate, 医学部, 助手 (40315487)
IWAKI Daisuke Sapporo Medical University School of medicine, Research Associate, 医学部, 助手 (10315492)
TAKAHASHI Hiroki Sapporo Medical University School of medicine, Associate Professor, 医学部, 助教授 (60231396)
NAGAE Hisato Yamasa Corporation Diagnostic Division, Director, 診断薬部, 主任
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| Project Period (FY) |
2000 – 2001
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| Keywords | alveolar type II cells / idiopathic interstitial pneumonia / SP-A / SP-D / radiation pneumonitis / autoantibody / Toll-like receptor / lung adenocarcinoma |
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| Research Abstract |
The purpose of this study was to pursue clinical application for pathophysiological analysis, diagnosis and treatment of lung diseases by genes and their products expressed in alveolar type II cells. We have identified the antigen to autoantibody existing in sera from patients with idiopathic interstitial pneumonia (IIP), established clinical significance of serum SP-A and SP-D as disease markers and applied lung collectins and pattern recognition receptors for treatment of respiratory infections.
(1) When A549 cell line was examined for immunoreactivity with sera from patients with IIP, approximately 50 % of patient sera reacted positively with A549 cells. Confocal microscopy revealed that the antigen recognized by patient sera localized in the cyoplasm of the cells. Patient IgG immunoprecipitaed 120 kDa protein. Proteome analysis of the 120 kDa protein identified the antigen as alanyl tRNA synthetase. We have cloned DNA for alanyl tRNA synthetase. When we analyzed immunocytochemically
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CHO cells which had been shown to be negative staining for patient IgG and were transfected with CDNA for this enzyme, patient IgG recognized the antigen in CHO cells that colocalized with GFP-labeled alanyl tRNA synthetase. In addition, sera from IIP patients significantly inhibited the enzyme activities of alanyl tRNA synthetase. These results clearly demonstrate that there exists antoantibody to alanyl tRNA synthetase in sera from IIP patients.
(2) Serum SP-A and SP-D increased in patients with radiation pneumonitis. SP-A and SP-D appeared to respond to the small lung damages which was able to detect by CT but not by chest Xp, demonstrating the serological usefulness of SP-A and SP-D as disease markers. In addition, we have establised the detection system of micrometastasis in peripheral blood in patients with lung adenocarcinoma using RT-PCR for SP-A, SP-C and CC10.
(3) We have analyzed the structure-function relationship of Toll-like receptor 2 that has been shown to interact with SP-A and SP-D. and identified the TLR2 region Ser40-Ile64 as the functional region in recognition and signal transduction of Staphylococcal peptidoglycan. Less
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