Sköld C M, Ohkuni Y, Liu X D, Numerof R, Rennard S I
Department of Internal Medicine, University of Nebraska Medical Center, Omaha, USA.
Inflammation. 2001 Feb;25(1):47-51. doi: 10.1023/a:1007075628316.
In the current study, we asked whether mast cells might modulate remodeling of extracellular matrix by affecting fibroblast-mediated contraction of three-dimensional collagen gels. Mast cells and human lung fibroblasts were co-cultured in floating type I collagen gels. The area of the gels was measured by an image analyzer. Mast cells in co-culture augmented fibroblast contractility (P < 0.001) in a time- and concentration dependent manner. The tryptase inhibitor bis(5-amidino-2-benzimidazo-lyl)methane (BABIM) were unable to block the augmented fibroblast contractility induced by co-cultured mast cells and tryptase added alone in the culture system had no effect on contractility, suggesting that other mediators besides tryptase might be involved. The amount of collagen in dissolved gels, measured as hydroxyproline, did not change after co-culture indicating that degradation of collagen may not be a major mechanism. Our findings support the hypothesis that the activity of mast cells may drive rearrangement of extracellular matrix and this and could subsequently lead to fibrosis and tissue dysfunction.
在本研究中，我们探究了肥大细胞是否可能通过影响成纤维细胞介导的三维胶原凝胶收缩来调节细胞外基质的重塑。肥大细胞与人肺成纤维细胞在漂浮的I型胶原凝胶中共培养。凝胶面积通过图像分析仪测量。共培养中的肥大细胞以时间和浓度依赖性方式增强了成纤维细胞的收缩性（P < 0.001）。色氨酸酶抑制剂双（5-脒基-2-苯并咪唑基）甲烷（BABIM）无法阻断共培养的肥大细胞诱导的增强的成纤维细胞收缩性，并且在培养系统中单独添加色氨酸酶对收缩性没有影响，这表明除色氨酸酶外可能还涉及其他介质。以羟脯氨酸衡量的溶解凝胶中的胶原量在共培养后没有变化，表明胶原降解可能不是主要机制。我们的研究结果支持以下假设：肥大细胞的活性可能驱动细胞外基质的重排，这随后可能导致纤维化和组织功能障碍。
