Howling Graeme I, Dettmar Peter W, Goddard Paul A, Hampson Frank C, Dornish Michael, Wood Edward J
Leeds Skin Research Centre, School of Biochemistry and Molecular Biology, University of Leeds, Leeds LS2 9JT, UK.
Biotechnol Appl Biochem. 2002 Dec;36(3):247-53. doi: 10.1042/ba20020040.
The effects of chitin [(1-->4)-2-acetamido-2-deoxy-beta-D-glucan] and its partially deacetylated derivatives, chitosans, on the human dermal fibroblast-mediated contraction of collagen lattices were examined in vitro as a model for the contraction of cutaneous wounds in vivo. Chitosan CL313A, a short-chain-length 89% deacetylated chitosan chloride, inhibited fibroblast-populated collagen lattice (FPCL) contraction at higher initial concentrations (500 and 1,000 microg/ml) in FPCLs fabricated with responsive dermal fibroblasts, while in FPCLs containing non-responsive fibroblasts inhibition of contraction was reduced. The responsive and non-responsive phenotype of human dermal fibroblasts to treatment with chitosan CL313A has been reported previously by us. The inhibition of fibroblast-mediated collagen lattice contraction by chitosan appeared to be strongly correlated with whether the cells were responsive or non-responsive. The effect of chitin-50A on fibroblast-mediated collagen lattice contraction was also examined to investigate whether the level of deacetylation was important for its inhibitory effect on contraction. However, this had no effect on contraction at the concentrations tested, supporting previous work that only chitosan samples with higher levels of deacetylation showed any biological activity. This work indicates that highly deacetylated chitosan inhibits fibroblast-mediated contraction of collagen lattices and may therefore be useful as a therapeutic agent to reduce contraction and therefore scarring in wound healing in vivo.
以几丁质[(1→4)-2-乙酰氨基-2-脱氧-β-D-葡聚糖]及其部分脱乙酰化衍生物壳聚糖为研究对象,体外检测其对人真皮成纤维细胞介导的胶原晶格收缩的影响,以此作为体内皮肤伤口收缩的模型。壳聚糖CL313A是一种短链长度、脱乙酰度为89%的氯化壳聚糖,在由反应性真皮成纤维细胞构建的成纤维细胞填充胶原晶格(FPCL)中,较高初始浓度(500和1000μg/ml)时可抑制其收缩,而在含有无反应性成纤维细胞的FPCL中,收缩抑制作用减弱。我们之前已报道过人真皮成纤维细胞对壳聚糖CL313A处理的反应性和无反应性表型。壳聚糖对成纤维细胞介导的胶原晶格收缩的抑制作用似乎与细胞是否有反应性密切相关。还检测了几丁质-50A对成纤维细胞介导的胶原晶格收缩的影响,以研究脱乙酰水平对其收缩抑制作用是否重要。然而,在所测试的浓度下,其对收缩无影响,这支持了之前的研究结果,即只有脱乙酰水平较高的壳聚糖样品才具有生物活性。这项研究表明,高度脱乙酰化的壳聚糖可抑制成纤维细胞介导的胶原晶格收缩,因此可能作为一种治疗剂,用于减少体内伤口愈合过程中的收缩及瘢痕形成。