Host defense mechanism by pulmonary surfactant proteins A and D thiir clinical application

本研究的目的是探讨肺表面活性蛋白SP-A和SP-D防御宿主的分子机制，并建立其临床应用。(1)将大鼠Thr174-Gly194的SP-A区域替换为Thr164-Asp184的MBP-A区域的SP-A/MBP-A嵌合体失去了DPPC结合、Ca2+依赖的GalCer结合以及与肺泡相互作用的SP-A功能。 II型细胞但获得了结合PI的MBP活性。对应于该SP-A区域的合成肽用于与LPS和肽聚糖相互作用。(2)SP-A和SP-D分别与CD14的肽部分和寡糖部分相互作用。 SP-A和SP-D改变了CD14与LPS的相互作用。(3)ARDS患者BAL液中SP-A水平显着下降，但SP-D水平没有显着下降。 SP-A水平不低的ARDS高危患者并未发展为ARDS。(4)血清SP-A和SP-D的检测反映了胶原血管疾病患者的微小间质病理改变，而这些改变可以通过胸部CT检测到，而通过胸部Xp无法检测到。(5)利用谷氨酰胺合成酶系统，利用CHO-K1细胞和pEE14载体，建立了重组SP-A和SP-D的大规模生产系统。(6)内容糖尿病大鼠BAL液中SP-A和SP-D的含量增加，表明SP-A和SP-D作为急性期反应物发挥作用。(7)通过SP-A/SP-D嵌合体分析，羧基末端25个氨基酸已被鉴定为SP-A和SP-D与其配体相互作用所必需的。(8)在原发性肺腺癌患者的骨髓中检测了SP-A的表达。 SP-A（免疫染色和mRNA）的表达与细胞角蛋白之间存在显着相关性。骨髓SP-A阳性的患者往往表现出较高的肿瘤纤维化和血管侵犯评分，野口分类为C-F型，提示SP-A表达可用于检测肺腺癌的微转移。较少的

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 … More 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