Human mast cells stimulate fibroblast proliferation, collagen synthesis and lattice contraction: a direct role for mast cells in skin fibrosis
Human mast cells stimulate fibroblast proliferation, collagen synthesis and lattice contraction: a direct role for mast cells in skin fibrosis
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DOI：
10.1046/j.1365-2222.2002.01293.x
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发表时间：
2002-02-01
影响因子：
6.1
通讯作者：
Levi-Schaffer, F
中科院分区：
文献类型：
--
作者：
Garbuzenko, E;Nagler, A;Levi-Schaffer, F
背景肥大细胞是皮肤速发型超敏反应的关键细胞，也被认为在影响皮肤的组织重塑和纤维化过程中起着重要作用。目的研究肥大细胞（human mast cells，HMC）在皮肤纤维化过程中的直接作用，通过评估人肥大细胞系HMC-1对人皮肤成纤维细胞的影响，方法将HMC-1超声处理物加入到人皮肤成纤维细胞中，并评估以下参数：增殖（[（3）H]-胸苷）、胶原合成（[（3）H]脯氨酸）、基质金属蛋白酶（MMPs）活性（酶谱）和金属蛋白酶组织抑制剂（TIMPs）（反向酶谱法），结果HMC-1的表达与胶原蛋白的表达呈负相关，与胶原蛋白的表达呈负相关。1超声处理显著增加了人皮肤成纤维细胞的增殖和胶原蛋白的产生，并且这些特性不受加热超声处理（56 ℃，30 min，或100 ℃，3 min）。两种主要的肥大细胞介质，组胺和类胰蛋白酶，被认为是负责增加成纤维细胞增殖和胶原蛋白的产生。HMC-1超声处理物没有显示任何预形成的明胶酶活性，并且其添加到成纤维细胞中没有改变它们的pro-MMP-2和MMP-2活性。另一方面，发现HMC-1具有TIMP-1和TIMP-2。加入HMC-1对成纤维细胞TIMP-1没有影响，但诱导TIMP-2活性呈剂量依赖性增加。此外，HMC-1声处理与成纤维细胞一起接种在三维胶原凝胶显着增强其contraction.Conclusion，我们已经表明，人肥大细胞，颗粒存储，因此快速释放介质，增加人皮肤成纤维细胞增殖，胶原合成，TIMP-2和胶原凝胶收缩。因此，肥大细胞在皮肤重塑和纤维化中具有直接和增强的作用。
Background Mast cells, the key cells of immediate hypersensitivity type reactions, have also been postulated to have a central role in influencing tissue remodelling and fibrosis occurring in the skin.Objective Our aim was to investigate the direct role of human mast cells (HMC) in skin fibrotic processes, by assessing the effects of the addition of the human mast cell line HMC-1 to human skin fibroblasts, and to identify the responsible mediators.Methods HMC-1 sonicates were added to human skin fibroblasts and the following parameters were evaluated: proliferation ([(3) H]-thymidine), collagen synthesis ([(3) H] proline), activity of matrix metalloproteinases (MMPs) (zymography) and tissue inhibitors of metalloproteinases (TIMPs) (reverse zymography), and collagen gel contraction.Results HMC-1 sonicate increased significantly both proliferation and collagen production in the human skin fibroblasts and these properties were not affected by heating of the sonicate (56 degreesC, 30 min, or 100 degreesC, 3 min). Two main mast cell mediators, histamine and tryptase, were found to be responsible for the increase in fibroblast proliferation and collagen production. HMC-1 sonicate did not display any pre-formed gelatinase activity, and its addition to the fibroblasts did not change their pro-MMP-2 and MMP-2 activity. On the other hand, HMC-1 were found to possess TIMP-1 and TIMP-2. Addition of HMC-1 had no effect on fibroblasts TIMP-1 but induced a dose-dependent increase of TIMP-2 activity. In addition, HMC-1 sonicate seeded together with the fibroblasts in tri-dimensional collagen gel significantly enhanced their contraction.Conclusion We have shown that human mast cells, by granule-stored and therefore quickly releasable mediators, increase human skin fibroblast proliferation, collagen synthesis, TIMP-2 and collagen gel contraction. Therefore, mast cells have a direct and potentiating role in skin remodelling and fibrosis.