Garbuzenko E, Nagler A, Pickholtz D, Gillery P, Reich R, Maquart F-X, Levi-Schaffer F
Department of Pharmacology, School of Pharmacy, Faculty of Medicine, The Hebrew University-Hadassah Medical School, PO 12065, Jerusalem 91120, Israel.
Clin Exp Allergy. 2002 Feb;32(2):237-46. doi: 10.1046/j.1365-2222.2002.01293.x.
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.
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.
HMC-1 sonicates were added to human skin fibroblasts and the following parameters were evaluated: proliferation ([3H]-thymidine), collagen synthesis ([3H] proline), activity of matrix metalloproteinases (MMPs) (zymography) and tissue inhibitors of metalloproteinases (TIMPs) (reverse zymography), and collagen gel contraction.
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 degrees C, 30 min, or 100 degrees C, 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.
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.
肥大细胞是速发型超敏反应的关键细胞，也被认为在影响皮肤组织重塑和纤维化过程中起核心作用。
我们的目的是通过评估将人肥大细胞系HMC-1添加到人皮肤成纤维细胞的效果，来研究人肥大细胞（HMC）在皮肤纤维化过程中的直接作用，并确定相关介质。
将HMC-1超声裂解物添加到人皮肤成纤维细胞中，并评估以下参数：增殖（[3H] - 胸腺嘧啶核苷）、胶原合成（[3H] - 脯氨酸）、基质金属蛋白酶（MMPs）活性（酶谱法）和金属蛋白酶组织抑制剂（TIMPs）（反向酶谱法）以及胶原凝胶收缩。
HMC-1超声裂解物显著增加了人皮肤成纤维细胞的增殖和胶原产生，并且这些特性不受超声裂解物加热（56℃，30分钟，或100℃，3分钟）的影响。发现两种主要的肥大细胞介质组胺和类胰蛋白酶是成纤维细胞增殖和胶原产生增加的原因。HMC-1超声裂解物未显示任何预先形成的明胶酶活性，并且将其添加到成纤维细胞中并未改变它们的前MMP-2和MMP-2活性。另一方面，发现HMC-1具有TIMP-1和TIMP-2。添加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，与成纤维细胞一起接种在三维胶原凝胶中的HMC-1超声裂解物显著增强了它们的收缩。
我们已经表明，人肥大细胞通过颗粒储存且因此可快速释放的介质，增加人皮肤成纤维细胞的增殖、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作用。
