Evaluations of Specific Endothelial Cell Markers in Lung Alveolar Capillaries

在健康和病理条件下，肺的肺泡毛细血管的形态已经有了很好的记录。然而，到目前为止，可用的结果可以概括为光镜和电子显微镜的普通观察，其功能含义远远不能令人满意。为了解释和评价肺泡毛细血管内皮细胞的表型活化，我们的观察一直集中在肺泡壁的单个毛细血管上。结合电子和共聚焦激光扫描显微镜，多种探测抗原，包括抗凝血凝血调节蛋白（TM）、凝血血管性血变因子（vWf）、蛋白酶激活受体（PAR）及其配体丝氨酸蛋白酶，已应用于人类和实验动物的肺部。重要的新发现如下：1)肺泡毛细血管内皮缺乏vWf的常规表达，但被TM完全覆盖；2)原发性肺腺癌肿瘤细胞破坏肺泡壁或转移肺泡壁时，肺泡壁发生从TM-显性表型向vwf -显性表型的免疫组织化学转化；3)内皮细胞附近肿瘤细胞引发的PAR促进了TM的丢失，vWf开始积累；4)凝血酶等丝氨酸蛋白酶对内皮细胞PAR的激活可发挥多种生物活性，包括肺泡壁细胞的细胞生长和胶原蛋白的生成。因此，肺泡毛细血管内皮细胞可能至少部分是修复肺泡损伤的主要刺激物。在这种联系下，肺泡毛细血管内皮细胞将深入参与促进肺泡壁细胞之间的细胞网络功能。我们的研究目标是进一步探讨内皮细胞在胶原血管病相关肺纤维化中的基本功能。

Morphology of the alveolar capillaries in the lung has been well documented under healthy and pathologic conditions. However, so-far available results could be summarized as plain observations by light and electron microscopies, and the functional implication derived from them is far from satisfactory. In order to explain and evaluate phenotypic activation of alveolar capillary endothelial cells, our observation has been focusing on a single unit capillary of alveolar walls in the lung. Together with electron and confocal laser scanning microscopies, multiple probing antigens, including anticoagulant thrombomodulin (TM), coagulant von Willebrand factor (vWf), protease-activated receptors (PAR) and their ligand-serine proteases, have been applied on human and experimental animal lungs. Important and novel findings we have obtained were as follows : 1) alveolar capillary endothelium lacked a conventional expression of vWf, but fully covered by TM ; 2) immunohistochemical conversion, from TM- to vWf-dominant phenotype, underwent when alveolar walls were damaged or metastasized by neoplastic cells of primary lung adenocarcinoma ; 3) PAR in endothelial cells elicited by nearby neoplastic cells facilitated a loss of TM while vWf started to accumulate ; and 4) activation of PAR on endothelial cells by serine proteases such as thrombin lead to exert a variety of biological activities, including cell growth and collagen production in alveolar wall cells. Thus, alveolar capillary endothelial cells might at least partly be a primary stimulator for repairing alveolar damages. In this connection alveolar capillary endothelial cells would be deeply involved in promoting cellular network functions among the alveolar wall cells. Our research aims are forwarding further to evaluate basic functions of endothelial cells in collagen vascular disease-related lung fibrosis.