A monoclonal antibody to the carboxyterminal domain of procollagen type I visualizes collagen-synthesizing fibroblasts. Detection of an altered fibroblast phenotype in lungs of patients with pulmonary fibrosis.
A monoclonal antibody to the carboxyterminal domain of procollagen type I visualizes collagen-synthesizing fibroblasts. Detection of an altered fibroblast phenotype in lungs of patients with pulmonary fibrosis.
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I 型原胶原羧基末端结构域的单克隆抗体使合成胶原的成纤维细胞可视化。
DOI：
10.1172/jci112707
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发表时间：
1986
期刊：
影响因子：
--
通讯作者：
Kuhn3rd,C
中科院分区：
文献类型：
--
作者：
McDonald,JA;Broekelmann,TJ;Matheke,ML;Crouch,E;Koo,M;Kuhn3rd,C
过度的胶原沉积在纤维化的发展中起着关键作用，并且早期或活动性纤维化可能比瘢痕形成的后期阶段更容易受到治疗干预。然而，目前还没有简单的方法来评估人体组织中成纤维细胞的胶原合成和分泌活性。I型前胶原羧基末端结构域在胶原分泌期间被蛋白水解除去。因此，针对这些结构域的抗体应该染色合成I型胶原的成纤维细胞，而不是可能掩盖来自细胞的信号的细胞外胶原原纤维。我们开发和特点的单克隆抗体（抗-PC）的羧基末端前肽的I型前胶原特异性。为了确定Anti-pC染色与胶原合成的关系，我们对胚胎和成年鸡肌腱进行了染色。鸡胚肌腱成纤维细胞积极合成I型胶原蛋白染色与抗-pC，而静止的成人肌腱成纤维细胞没有染色与抗-pC。受伤的成人肌腱成纤维细胞，在伤口部位与抗pC染色。因此，Anti-pC特异性地使活跃合成胶原的成纤维细胞可视化。来自纤维化肺病患者的肺活检用抗pC染色。间质和肺泡内成纤维细胞活组织检查的活动性纤维化患者强烈染色的抗pC，而正常人肺未染色。正常肺中染色的缺乏支持了纤维化与组织成纤维细胞的胶原合成表型改变相关的假设。抗pC抗体可能为评估组织损伤部位的纤维化活性提供有用的临床工具。
Excessive collagen deposition plays a critical role in the development of fibrosis, and early or active fibrosis may be more susceptible to therapeutic intervention than later stages of scarring. However, at present there is no simple method for assessing the collagen-synthesizing and secreting activity of fibroblasts in human tissues. Type I procollagen carboxyterminal domains are proteolytically removed during collagen secretion. Thus, antibodies to these domains should stain fibroblasts synthesizing type I collagen but not extracellular collagen fibrils which could mask the signal from the cells. We developed and characterized a monoclonal antibody (Anti-pC) specific for the carboxyterminal propeptide of type I procollagen. To determine the relationship between Anti-pC staining and collagen synthesis, we stained embryonic and adult chicken tendon. Embryonic chick tendon fibroblasts actively synthesizing type I collagen stained heavily with Anti-pC, while quiescent adult tendon fibroblasts did not stain with Anti-pC. Wounded adult tendons developed fibroblasts that stained with Anti-pC at the wound site. Thus, Anti-pC specifically visualized fibroblasts actively synthesizing collagen. Lung biopsies from patients with fibrotic lung disease were stained with Anti-pC. Interstitial and intraalveolar fibroblasts in biopsies from patients with active fibrosis stained intensely with Anti-pC, while normal human lung was unstained. The absence of staining in normal lung supports the hypothesis that fibrosis is associated with an altered collagen-synthesizing phenotype of tissue fibroblasts. Anti-pC may provide a useful clinical tool for assessing fibrogenic activity at sites of tissue injury.Images