CHARACTERIZATION OF THE PATHOGENESIS OF LYMPHANGIOLEIOMYOMATOSIS (LAM)

肺淋巴管肌瘤病(LAM)是一种罕见的疾病， 几乎只发生在育龄妇女身上。临床部 LAM的表现相当独特，包括复发性 自发性气胸、乳糜胸、咯血、乳糜性腹水和 缓慢进行性呼吸困难。主要的组织病理学发现是 看起来不成熟、杂乱无章的流畅显著扩散 肺中的肌肉细胞和胸腔中沿轴淋巴管的肌肉细胞 腹部。LAM的大多数临床症状和体征可能是 由于异常平滑的细胞增殖。异常的平滑肌 LAM中的细胞更短、更饱满，核与核的比率更高 胞浆比正常的平滑肌细胞大。有趣的是，这些异常 平滑肌细胞，与呼吸道或血液中的正常细胞不同 血管，与单抗HMB45反应，HMB45与100- 在人类黑色素瘤细胞中发现的KDA糖蛋白(称为gp100)。至 鉴定HMB45识别的抗原，正常人肺组织， 4例LAM患者的肺标本和3例黑色素瘤的细胞 细胞系(Malme-3M、A2058和CHL-1)经Northern 分析、免疫组织化学和电子显微镜研究 使用全长gp100 cDNA探针进行Northern分析 提取总RNA的逆转录-聚合酶链式反应 来自Malme-3M细胞。在Malme-3M细胞中gp100基因的表达水平最高， 其次是A2058细胞，然后是LAM个体的肺组织； 在正常肺和CHL-1细胞中均未检测到。免疫组织化学 HMB45在Malme-3M细胞中表达较强，而在A2058细胞中表达较少 和LAM患者的肺组织。HMBYS反应性；它不是 在正常肺或CHL-1细胞中检测到。电子致密小颗粒 异常平滑肌细胞胞浆内有细小的板层结构 用电子显微镜观察肺组织中细胞的变化。这些颗粒 类似于Malme-3M细胞中未成熟的黑素小体。此外，这些 电子致密颗粒含有HMB45结合位点 免疫电子显微镜。

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.