CHARACTERIZATION OF THE PATHOGENESIS OF LYMPHANGIOLEIOMYOMATOSIS (LAM)

淋巴管平滑肌瘤病 (LAM) 发病机制的特征

• 批准号: 2441409
• 负责人: J MOSS
• 金额: --
• 依托单位: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2441409
• 关键词: antigen antibody reaction; ascites; cellular pathology; clinical research; dyspneas; glycoproteins; histopathology; human subject; immunocytochemistry; immunoelectron microscopy; leiomyoma; lung; monoclonal antibody; northern blottings; oncoproteins; pneumothorax disorder; respiratory reflex; smooth muscle

Pulmonary lymphangioleiomyomatosis (LAM) is an uncommon disorder that occurs almost exclusively in women of childbearing age. The clinical presentation of LAM is quite distinctive and includes recurrent spontaneous pneumothorax, chylothorax, hemoptysis, chylous ascites and slowly progressive dyspnea. The cardinal histopathologic finding is a remarkable proliferation of immature-appearing, disorganized smooth muscle cells in the lung and along axial lymphatics in the thorax and abdomen. It is likely that most clinical symptoms and signs of LAM are due to abnormal smooth cell proliferation. The abnormal smooth muscle cells in LAM are shorter, plumper, and have a higher ratio of nucleus to cytoplasm than normal smooth muscle cells. Interestingly, these abnormal smooth muscle cells, unlike their normal counterparts in airways or blood vessels, react with monoclonal antibody HMB45, which reacts with a 100- kDa glycoprotein (termed gp100) found in human melanoma cells. To characterize the antigens recognized by HMB45, normal human lung tissue, lung specimens from four patients with LAM, and cells from three melanoma cell lines (Malme-3M, A2058, and CHL-1) were subjected to Northern analysis, immunohistochemical and electron microscopic studies as well as Northern analysis using a full-length gp100 cDNA probe generated by reverse transcription-polymerase chain reaction from total RNA isolated from Malme-3M cells. Levels of gp100 mRNA were highest in Malme-3M cells, followed by A2058 cells, and then lung tissue of individuals with LAM; it was not detected in normal lung or CHL-1 cells. Immunohistochemical staining for HMB45 was intense in Malme-3M cells, and less in A2058 cells and lung tissue of individuals with LAM. HMBYS reactivity; it was not detected in normal lung or CHL-1 cells. Electron-dense small granules with a fine lamellar structure in the cytoplasm of abnormal smooth muscle cells in LAM lung were detected by electron microscopy. These granules resembled immature melanosomes in Malme-3M cells. Further, these electron-dense granules contained HMB45-binding sites as demonstrated by immunoelectron microscopy.

肺淋巴管肌瘤病（LAM）是一种罕见的疾病， 几乎完全发生在育龄妇女中。临床 林的介绍非常独特，包括经常性 自发性气胸，乳沟，heles舌，吟cer骨和 缓慢进行性呼吸困难。基本组织病理学发现是 未成熟，杂乱无章的平滑的显着增殖 肺中的肌肉细胞以及胸部和轴向淋巴管 腹部。大多数临床症状和林的迹象可能是 由于平滑细胞增殖异常。平滑肌异常 LAM中的细胞较短，浓缩剂，核与核的比率更高 细胞质比正常平滑肌细胞。有趣的是，这些异常 平滑肌细胞与气道或血液中的正常对应物不同 血管与单克隆抗体HMB45反应，该抗体与100- 在人黑色素瘤细胞中发现的KDA糖蛋白（称为GP100）。 到 表征由正常人肺组织HMB45识别的抗原， 来自四名LAM患者的肺标本和三个黑色素瘤的细胞 细胞系（Malme-3M，A2058和CHL-1）受到北部 分析，免疫组织化学和电子显微镜研究 作为北方分析，使用由全长GP100 cDNA探针产生的 总RNA分离的逆转录 - 聚合酶链反应 来自Malme-3M细胞。在Malme-3M细胞中，GP100 mRNA的水平最高， 然后是A2058细胞，然后是LAM个体的肺组织； 在正常的肺或CHL-1细胞中未检测到它。 免疫组织化学 HMB45的染色在Malme-3M细胞中的染色很强，而A2058细胞中的染色较少 和患有LAM的个体的肺组织。 HMBYS反应性；不是 在正常肺或CHL-1细胞中检测到。电子密集的小颗粒 在异常平滑肌的细胞质中具有细层状结构 通过电子显微镜检测到LAN肺中的细胞。 这些颗粒 在Malme-3M细胞中类似于未成熟的黑素体。此外，这些 电子致密颗粒包含HMB45结合位点，如 免疫电子显微镜。