Pardo J, Diaz L, Errasti P, Idoate M, de Alava E, Sola I, Lozano L, Panizo A
Department of Pathology, Clínica Universitaria, University of Navarra, Pamplona, Spain.
Virchows Arch. 2000 Aug;437(2):167-72. doi: 10.1007/s004280000211.
An increased number of mast cells (MCs) is found in renal specimens of patients with diseases associated with persistent chronic inflammation. MCs proliferation is partly dependent on the presence of T lymphocytes. Both chronic inflammation and T-lymphocytes are essential in the development of chronic rejection (CR), and probably for the infiltration of MCs. MC-derived products such as heparin, histamine, and serine proteases may be responsible for endothelial proliferation and excess collagen production by fibroblasts. In this study, a quantitative evaluation of the MCs infiltration in kidney allografts with CR is performed. The extent of renal fibrosis was analysed in samples stained with Masson's trichrome. To evaluate the potential relationship between MCs and fibrosis in CR we analysed 30 kidneys with CR (25 from nephrectomies and 5 from autopsies). Ten transplanted kidneys obtained from patients died by causes not related with rejection were used as controls. CR was graded according to the Banff schema, which assesses the degree of vasculopathy, tubular atrophy, interstitial fibrosis and transplantation glomerulopathy. Giemsa-stained sections and immunohistochemistry using anti-MC tryptase and c-kit monoclonal antibodies were used to detect MCs. The mean number of MCs per 20 high-power fields (HPF) in the transplanted kidney with CR was 101.8+/-15.3 in the renal cortex and 46.60+/-6.52 in the medulla. MCs were significantly more numerous in CR with respect to normal kidneys, both in the cortex (P<0.01; Mann-Whitney U test) and in the medulla (P<0.01; Mann-Whitney U test). There was a positive correlation between the number of MCs and extent of fibrosis (P<0.01; Kruskal-Wallis one-way anova test) and tubular atrophy (P<0.01). These results suggest that MCs may play a role in the process of development of interstitial fibrosis in CR.
在患有持续性慢性炎症相关疾病的患者肾脏标本中，发现肥大细胞（MCs）数量增加。MCs增殖部分依赖于T淋巴细胞的存在。慢性炎症和T淋巴细胞在慢性排斥反应（CR）的发生发展中都至关重要，可能也是MCs浸润的原因。MCs衍生的产物，如肝素、组胺和丝氨酸蛋白酶，可能是导致内皮细胞增殖和成纤维细胞过度产生胶原蛋白的原因。在本研究中，对发生CR的同种异体肾移植中MCs浸润情况进行了定量评估。用Masson三色染色法对样本进行分析，以确定肾纤维化程度。为了评估CR中MCs与纤维化之间的潜在关系，我们分析了30个发生CR的肾脏（25个来自肾切除术，5个来自尸检）。将10个因与排斥反应无关的原因死亡的患者的移植肾用作对照。根据Banff标准对CR进行分级，该标准评估血管病变、肾小管萎缩、间质纤维化和移植性肾小球病的程度。使用吉姆萨染色切片以及抗MC类胰蛋白酶和c-kit单克隆抗体进行免疫组织化学检测MCs。发生CR的移植肾中，肾皮质每20个高倍视野（HPF）的MCs平均数量为101.8±15.3，髓质为46.60±6.52。与正常肾脏相比，CR肾脏中的MCs在皮质（P<0.01；Mann-Whitney U检验）和髓质（P<0.01；Mann-Whitney U检验）中均显著增多。MCs数量与纤维化程度（P<0.01；Kruskal-Wallis单因素方差分析）和肾小管萎缩（P<0.01）之间存在正相关。这些结果表明，MCs可能在CR间质纤维化的发生过程中起作用。
