Kuhn C, Mason R J
Department of Pathology, Brown University, Pawtucket, Rhode Island, USA.
Am J Pathol. 1995 Dec;147(6):1759-69.
Several biochemically unrelated multifunctional extracellular proteins, SPARC, thrombospondin 1, and tenascin-C (TN), have been grouped as antiadhesive glycoproteins because they inhibit the spreading of cells on extracellular matrix in vitro. Migration of fibroblasts and epithelial cells into the air spaces to organize inflammatory exudate is a feature common to several fibrosing lung diseases. We hypothesized that migration would be facilitated by loosening the adhesive interactions between cells and the pericellular matrix components of the alveolar wall and that one or more of the anti-adhesive glycoproteins could be involved. Immunohistochemistry was used to localize SPARC, TN, and thrombospondin 1 in biopsies of organizing pneumonia, idiopathic pulmonary fibrosis (nine cases of usual interstitial pneumonia, one of desquamative interstitial pneumonia), and control lungs. Each antigen had a distinctive distribution. Only TN was expressed in control lungs, where it strongly stained the basement membrane of large bronchi and weakly stained alveolar entrance rings and small veins. In organizing pneumonia, TN was heavily stained through the entire extracellular matrix of the Masson bodies. In idiopathic pulmonary fibrosis, TN was abundant in the fibroblast foci of active fibrosis but was also present in the basement membrane regions beneath the metaplastic epithelium lining honeycomb cysts. TN was abundant in the interstitium in desquamative interstitial pneumonia. SPARC was observed only intracellularly where it occurred in the fibroblasts of Masson bodies of organizing pneumonia and the fibroblast foci of usual interstitial pneumonia. In desquamative interstitial pneumonia, expression of SPARC was minimal, in rare interstitial fibroblasts. Thrombospondin 1 was found consistently in organizing pneumonia but only infrequently in idiopathic pulmonary fibrosis. In both, it was localized in the extracellular matrix immediately beneath reparative epithelium. These results are consistent with a role for SPARC in fibroblast migration. TN may function in both fibroblast migration and the adhesion of metaplastic bronchial-type epithelium. However, these proteins also have other activities that may be important in pulmonary fibrosis. The localization of thrombospondin 1 suggests that it may be synthesized by regenerating epithelium where it may aid in the adhesion or migration of the epithelial cells.
几种生化性质不相关的多功能细胞外蛋白，如骨连接蛋白（SPARC）、血小板反应蛋白1和腱生蛋白-C（TN），已被归类为抗黏附糖蛋白，因为它们在体外可抑制细胞在细胞外基质上的铺展。成纤维细胞和上皮细胞迁移至气腔以组织炎性渗出物是几种肺纤维化疾病的共同特征。我们推测，通过减弱细胞与肺泡壁周细胞基质成分之间的黏附相互作用可促进迁移，并且可能涉及一种或多种抗黏附糖蛋白。采用免疫组织化学方法在机化性肺炎、特发性肺纤维化（9例普通间质性肺炎、1例脱屑性间质性肺炎）及对照肺组织活检标本中定位SPARC、TN和血小板反应蛋白1。每种抗原都有独特的分布。仅TN在对照肺组织中表达，它强烈染色大支气管的基底膜，而肺泡入口环和小静脉染色较弱。在机化性肺炎中，TN在Masson小体的整个细胞外基质中均有重度染色。在特发性肺纤维化中，TN在活动性纤维化的成纤维细胞灶中丰富，但也存在于蜂窝状囊肿内衬化生上皮下方的基底膜区域。在脱屑性间质性肺炎的间质中TN丰富。仅在机化性肺炎的Masson小体的成纤维细胞和普通间质性肺炎的成纤维细胞灶的细胞内观察到SPARC。在脱屑性间质性肺炎中，SPARC表达极少，仅在罕见的间质成纤维细胞中表达。血小板反应蛋白-1在机化性肺炎中始终存在，但在特发性肺纤维化中仅偶尔出现。在这两种疾病中，它都定位于修复上皮下方的细胞外基质中。这些结果与SPARC在成纤维细胞迁移中的作用一致。TN可能在成纤维细胞迁移和化生支气管型上皮的黏附中均发挥作用。然而，这些蛋白还具有其他可能在肺纤维化中起重要作用的活性。血小板反应蛋白1的定位表明它可能由再生上皮合成，在那里它可能有助于上皮细胞的黏附或迁移。
