PULMONARY SURFACTANT ASSOCIATED PROTEINS AND RELATED C-TYPE LECTINS IN THE LUNG

肺透明膜病是中国最常见的急性肺损伤类型。 新生儿期。表面活性物质缺乏或功能受损 被证明是其发病机制中的重要组成部分。如果恢复正常 不会发生在生命的第一周，一种慢性损伤状态 持续修复(支气管肺发育不良，BPD)。两份甘露糖- 特定的同源凝集素已定位于肺。II型细胞 合成和分泌表面活性物质相关蛋白A(SP-A)。建议 SP-A的功能包括磷脂清除和再循环， 细菌的调理作用和补体固定。肺泡巨噬细胞 (Mphi)合成并在其表面表达甘露糖特异的内细胞膜 受体(MR)。MR参与胞外酶的清除。 和病原体，并已被认为参与识别和 Mphi对SP-A/细菌复合体的摄取三种额外的表面活性剂 相关蛋白已被鉴定为：SP-B、SP-C和SP-D。SP-B和 SP-C促进磷脂的快速表面吸收，并建议 参与表面活性物质脂质的回收利用。有证据表明 SP-D也是一种肺凝集素。使用广泛的法线库 人胎肺和新生儿肺及其他组织 急性肺损伤(HMD)，修复正常和异常 修复(BPD)，我们将使用免疫组织化学方法对SP-A、SP-B和 SP-C前体与肺组织分期的相关性 发展、肺损伤的存在和肺修复的阶段。 使用原位杂交技术，我们将定位每个基因的mrna 这些蛋白质中。此外，我们还将相关基因的表达 随着肺发育阶段、肺损伤的出现，以及 肺修复阶段。我们将确定气管、支气管内的细胞 腺体和传导性呼吸道上皮免疫组织化学 原位杂交法检测SP-A的表达。 我们将使用携带嵌合基因的转基因小鼠，该基因由5‘ 人SP-C基因与氯霉素连锁的侧翼序列 乙酰转移酶基因在细胞、组织中的定位研究 SP-C基因表达及其调控元件的分布和个体发育 利用分离的大鼠肺泡巨噬细胞，我们将研究MR的作用 在识别和清除SP-A和SP-A/脂质复合体方面。vbl.使用 分离的大鼠肺泡巨噬细胞我们将观察SP-A对 加强细菌清除，以确定摄入是否为受体- 调解，并开始初步表征/鉴定 受体参与，测试甘露聚糖抑制过程，并确定 甘露糖受体参与其中。

Hyaline membrane disease is the most common type of acute lung injury in the newborn period. Surfactant deficiency or impaired function has been shown to be an important component in its pathogenesis. If normal healing does not occur in the first week of life, a chronic state of injury and continuing repair occurs (bronchopulmonary dysplasia, BPD). Two mannose- specific homologous lectins have been localized to the lung. Type II cells synthesize and secrete surfactant-associated protein A (SP-A). Proposed functions for SP-A include phospholipid clearance and recycling, opsonization of bacteria, and complement fixation. Alveolar macrophages (Mphi) synthesize and express on their surface a mannose-specific endocytic receptor (MR). The MR is involved in clearance of extracellular enzymes and pathogens and has been suggested to be involved in recognition and uptake of SP-A/bacterial complexes by Mphi. Three additional surfactant associated proteins have been identified: SP-B, SP-C, and SP-D. SP-B and SP-C promote rapid surface absorption of phospholipids, and are suggested to be involved in recycling of surfactant lipid. There is evidence that SP-D is also a pulmonary lectin. Using an extensive library of normal human fetal lungs and of lungs and other tissues of newborn infants with acute lung injury (HMD), those with normal repair and those with abnormal repair (BPD), we will use immunohistochemistry to localize SP-A, SP-B and SP-C precursor and correlate our findings with the stage of lung development, the presence of lung injury and the stage of lung repair. Using in situ hybridization techniques, we will localize the mRNA for each of these proteins. In addition, we will correlate the expression of mRNA with the stage of lung development, the presence of lung injury, and the stage of lung repair. We will determine whether cells in tracheobronchial glands and conducting airway epithelia which are immunohistochemically stained for SP-A express mRNA for SP-A by in situ hybridization studies. We will use transgenic mice that carry a chimeric gene consisting of the 5' flanking sequences of the human SP-C gene linked to the chloramphenicol acetyl transferase gene to study the cellular localization, tissue distribution and ontogeny of SP-C gene expression and its control elements. Using isolated rat alveolar macrophages, we will examine the role of the MR in recognition and clearance of SP-A and SP-A/lipid complexes. Using isolated rat alveolar macrophages we will look at the ability of SP-A to enhance bacterial clearance, to determine if ingestion is receptor- mediated, and to begin initial characterization/identification of the receptor involved, test for mannan inhibitable processes and determine if the mannose receptor is involved.