AN IMMUNOHISTOCHEMICAL STUDY OF ARCHITECTURAL REMODELING AND CONNECTIVE-TISSUE SYNTHESIS IN PULMONARY FIBROSIS
AN IMMUNOHISTOCHEMICAL STUDY OF ARCHITECTURAL REMODELING AND CONNECTIVE-TISSUE SYNTHESIS IN PULMONARY FIBROSIS
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DOI：
10.1164/ajrccm/140.6.1693
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发表时间：
1989-12-01
期刊：
影响因子：
--
通讯作者：
MCDONALD, JA
中科院分区：
文献类型：
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作者：
KUHN, C;BOLDT, J;MCDONALD, JA
健康成人肺的成纤维细胞处于静止状态，合成少量胶原蛋白。我们研究了30例肺纤维化患者的肺活检，使用免疫组织化学与针对I型胶原前肽的单克隆抗体来定位主动合成胶原的成纤维细胞。相邻切片用III型和IV型胶原、纤维蛋白、细胞角蛋白、血浆纤维连接蛋白或含有ediia的“细胞”纤维连接蛋白（cFN）抗体染色。在快速肺纤维化中，包括弥漫性肺泡损伤的增殖期、组织性肺炎和亚急性特发性纤维化，胶原合成细胞在组织性渗出物填充空气中大量存在，但在肺泡壁间质、小叶间隔和血管壁中也可见到胶原合成细胞。在空气中沉积的新基质还含有III型胶原蛋白和含有ediia的纤维连接蛋白。在慢性肺纤维化中，超过一半的活检显示胶原合成灶和cFN沉积在空气-组织界面附近。病灶始终定位于基底层残余物外，因此在空气空间内。结果表明：(1)慢性特发性肺纤维化的纤维化与急性肺损伤后的纤维化一样，主要是由间隙内渗出物的组织引起的；(2)在此过程中，成纤维细胞协调增加胶原和纤维连接蛋白的合成。活性基质沉积灶为慢性肺纤维化的进行性提供了证据。
Fibroblasts in healthy adult lung are quiescent, synthesizing little collagen. We studied lung biopsies from 30 patients with pulmonary fibrosis, using immunohistochemistry with monoclonal antibodies against the propeptides of type I collagen to localize fibroblasts actively synthesizing collagen. Adjacent sections were stained with antibodies to type III and IV collagen, fibrin, cytokeratin, plasma fibronectin, or EDIIIa-containing “cellular” fibronectin (cFN). In rapid pulmonary fibrosis, including the proliferative phase of diffuse alveolar damage, organizing pneumonia, and subacute idiopathic fibrosis, collagen-synthesizing cells were numerous in organizing exudate filling airspaces but were also seen in the interstitium of the alveolar walls, interlobular septa, and walls of blood vessels. The new matrix deposited in the airspaces also contained type III collagen and EDIIIa-containing fibronectin. In chronic pulmonary fibrosis, more than half of the biopsies showed foci of collagen synthesis and cFN deposition near the air-tissue interface. The foci were consistently localized outside remnants of basal lamina and therefore within airspaces. The results indicate that (1) fibrosis in chronic idiopathic pulmonary fibrosis results mainly from organization of exudate within airspaces, just as it does after acute lung injury, and (2) during this process, fibroblasts increase their synthesis of collagen and fibronectin coordinately. Foci of active matrix deposition provide evidence for the progressive nature of chronic pulmonary fibrosis.