Grant-in-Aid for Scientific Research (B)
Respiratory organ internal medicine
|Sapporo Medical University
AKINO Toyoaki Sapporo Medical University School of Medicine Dept. of Biochemistry, Professor, 医学部, 教授 (80045377)
NAGATA Atsuo Yamasa Syouyu Co. , Laboratory of Immunological Diagnostics, Research Director, 診断薬部免疫研究室, 主任研究員 (00129157)
MATSUURA Eiji Yamasa Syouyu Co. , Laboratory of Immunological Diagnostics, Research Associate, 診断薬部免疫研究室, 主任研究員
SOHMA Hitoshi Sapporo Medical University School of Medicine Dept. of Biochemistry, Assistant P, 医学部, 講師 (70226702)
KUROKI Yoshio Sapporo Medical University School of Medicine Dept. of Biochemistry, Associate P, 医学部, 助教授 (70161784)
|Project Period (FY)
1995 – 1996
Completed (Fiscal Year 1996)
|Budget Amount *help
¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1996: ¥1,600,000 (Direct Cost: ¥1,600,000)
|Pulmonary Surfactant / Surfactant apoprotein / Gene analysis / Diffuse lung disease / Lung adenocarcinoma / SP-A / SP-D / SP-D / 肝サーファクタント
Pulmonary surfactant is a complex mixture of lipids and proteins existed in the alveoli. It is produced, secreted and reutilized by alveolar type II cells, and there is a metabolic cycle of the surfactant components between alveolar type II cells and alveolar space. There are four specific apoproteins, SP-A,SP-B,SP-C and SP-D in the lung surfactant, which are thought to be important for specific functions of the surfactant. Particularly, hydrophilic apoproteins SP-A and SP-D have the regulatory function of the metaoblic cycle. Changes in the metabolism of the surfactant components or in the production due to the gene expression may appear in various lung diseases. Recently mAbs to the apoproteins were prepared, and used as a marker of surfactant, and cDNAs of the apoproteins were isolated and study on the gene expressions is now possible. Therefore, this study focussed upon to investigate clinical usefulness of the surfactant apoproteins assay in respiratory diseases.
1. We developed a
simple ELISA kit for the determination of human SP-D for the clinical use. The ELISA was applied to sera from patients with respiratory diseases. The concentrations of SP-D in sera were prominently increased in patients with idiopathic pulmonary fibrosis (IPF), interstitial pneumonia with collagen disease (IPCD) and pulmonary alveolar proteinosis (PAP). The great majority of the patients with IPF,IPCD and PAP exhibited serum SP-D levels that exceeded the cut-off value (110 ng/ml). The measurement of SP-D in sera can provide a useful clinical marker for the diagnosis of these three diseases.
2. The gene expression of SP-A mRNA was examined in cancer cells from pleural effusions of patients with lung carcinomas, and it was specific for primary lung adenocarcinomas, and detected in none of other types of lung carcinomas. The SP-A mRNA detection in primary lung adenocarcinoma was much higher than the protein detection by immunohistochemistry. Therefore, the detection of SP-A mRNA in cells from pleural effusions is very helpful for the diagnosis of primary lung adenocarcinoma. 2) The acute lung injury by tracheal administration of LPS (endotoxin) induced the marked proliferation of alveolar epithelial cells in association with the concurrently increased SP-A,SP-B and SP-C mRNA.The overexpression of the gene expression may reflect the repair process of the damaged alveoli afetr acute lung injury.
3. Abnormal multimerized form of SP-A molecule are accumulated in the alveoli of patients with PAP,this unusual subpopulation of SP-A oligomer exhibits abnormal functions on tubular myelin formation and on biological activities induced by its receptor binding to alveolar type II cells. The molecular abnormality of SP-A may cause tremendes accumulation of surfactant in the alveoli of patients with PAP. Less