Riekki Riitta, Harvima Ilkka T, Jukkola Arja, Risteli Juha, Oikarinen Aarne
Department of Dermatology, University of Oulu, Oulu, Finland.
Exp Dermatol. 2004 Jun;13(6):364-71. doi: 10.1111/j.0906-6705.2004.00164.x.
Fibrosis is a common complication of radiotherapy. The pathogenesis of radiation-induced fibrosis is not known in detail. There is increasing evidence to suggest that mast cells contribute to various fibrotic conditions. Several mast-cell mediators have been proposed to have a role in fibrogenesis. Tryptase and chymase, the predominant proteins in mast cells, have been shown to induce fibroblast proliferation and collagen synthesis in vitro. In order to explore the role of mast cells in irradiation-induced fibrosis, we analyzed skin biopsies and suction blister fluid (SBF) samples from the lesional and healthy-looking skin of 10 patients who had been treated for breast cancer with surgery and radiotherapy. The biopsies were analyzed histochemically for mast-cell tryptase, chymase, kit receptor, and tumor necrosis factor-alpha. Skin collagen synthesis was assessed by determining the levels of type I and III procollagen amino-terminal propeptides (PINP and PIIINP) in SBF and using immunohistochemical staining for PINP. Immunohistochemical stainings for prolyl-4-hydroxylase reflecting collagen synthesis and chymase immunoreactivity in irradiated and control skin were also performed. The mean level of procollagen propeptides in SBF, which reflects actual skin collagen synthesis in vivo, was markedly increased in irradiated skin compared to corresponding healthy control skin areas. The mean number of PINP-positive fibroblasts was also significantly increased in the upper dermis of radiotherapy-treated skin. The number of cells positive for tryptase, chymase and kit receptor was markedly increased in irradiated skin. In addition, using double-staining techniques, it was possible to demonstrate that in some areas of the dermis, tryptase-positive mast cells and fibroblasts are closely associated. These findings suggest a possible role of mast cells in enhanced skin collagen synthesis and fibrosis induced by radiotherapy.
纤维化是放射治疗的常见并发症。辐射诱导纤维化的发病机制尚不清楚。越来越多的证据表明肥大细胞与多种纤维化疾病有关。几种肥大细胞介质被认为在纤维生成中起作用。肥大细胞中的主要蛋白质类胰蛋白酶和糜蛋白酶已被证明在体外可诱导成纤维细胞增殖和胶原蛋白合成。为了探究肥大细胞在辐射诱导纤维化中的作用，我们分析了10例接受过乳腺癌手术和放疗患者病变皮肤及外观正常皮肤的皮肤活检样本和水疱抽吸液（SBF）样本。对活检样本进行组织化学分析，检测肥大细胞类胰蛋白酶、糜蛋白酶、kit受体和肿瘤坏死因子-α。通过测定SBF中I型和III型前胶原氨基末端前肽（PINP和PIIINP）的水平并使用PINP免疫组化染色来评估皮肤胶原蛋白合成。还对受照射皮肤和对照皮肤进行了反映胶原蛋白合成的脯氨酰-4-羟化酶免疫组化染色和糜蛋白酶免疫反应性检测。与相应的健康对照皮肤区域相比，受照射皮肤中反映体内实际皮肤胶原蛋白合成的SBF中前胶原前肽的平均水平显著升高。放疗后皮肤的真皮上层中PINP阳性成纤维细胞的平均数量也显著增加。受照射皮肤中类胰蛋白酶、糜蛋白酶和kit受体阳性细胞的数量明显增加。此外，使用双重染色技术可以证明，在真皮的某些区域，类胰蛋白酶阳性肥大细胞和成纤维细胞紧密相关。这些发现表明肥大细胞可能在放疗诱导的皮肤胶原蛋白合成增强和纤维化中发挥作用。
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