KL-6, a human MUC1 mucin, is chemotactic for human fibroblasts
KL-6, a human MUC1 mucin, is chemotactic for human fibroblasts
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DOI：
10.1165/ajrcmb.17.4.2253
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发表时间：
1997-10-01
影响因子：
6.4
通讯作者：
Hiwada, K
中科院分区：
文献类型：
--
作者：
Hirasawa, Y;Kohno, N;Hiwada, K
血清和支气管肺泡灌洗液中的KL-6已被报道是指示纤维化肺疾病活动的敏感标志物。根据免疫组化和细胞计数研究的结果，该分子聚集在MUC 1粘蛋白中。为了阐明KL-6在纤维化肺疾病中的致病作用，我们表征了其生化特性，并使用改良的Boyden室检测了纯化的KL-6是否对体外人成纤维细胞具有趋化性。纯化的KL-6的生化性质与以前报道的其他MUC 1粘蛋白的生化性质相似。KL-6促进5/5的人肺成纤维细胞和3/4的人皮肤成纤维细胞的迁移。生物板分析表明KL-6具有趋化性和趋化动力学。虽然血小板衍生生长因子，成纤维细胞生长因子，或纤连蛋白也趋化成纤维细胞在实验系统中，只有纤连蛋白增强KL-6诱导的趋化性。这些观察结果表明KL-6是大多数成纤维细胞的趋化因子之一，并且小气道上皮衬里液中KL-6的增加可能导致纤维化肺病中的肺泡内纤维化。
KL-6 in serum and bronchoalveolar lavage fluid has been reported to be a sensitive marker indicating the activity of fibrosing lung diseases. The molecule is clustered in MUC1 mucin according to the findings of immunohistochemical and cytometric studies. To elucidate the pathogenic role of KL-6 in fibrosing lung disease, we characterized its biochemical properties and examined whether purified KL-6 is chemotactic for human fibroblasts in vitro using modified Boyden chambers. Biochemical properties of purified KL-6 were similar to those of other MUC1 mucins previously reported. KL-6 promoted the migration of 5 of 5 human lung fibroblasts and 3 of 4 human skin fibroblasts. Checkerboard analysis revealed that KL-6 was chemotactic as well as chemokinetic. Though platelet-derived growth factor, fibroblast growth factor, or fibronectin were also chemotactic for fibroblasts in the experimental system, only fibronectin augmented KL-6-induced chemotaxis. These observations indicate that KL-6 is one of the chemotactic factors for most fibroblasts and that the increased KL-6 in the epithelial lining fluid in small airways may cause the intra-alveolar fibrosis in fibrosing lung diseases.