Immunophenotypical Characterization of M1/M2 Macrophages and Lymphocytes in Cisplatin-Induced Rat Progressive Renal Fibrosis.
Immunophenotypical Characterization of M1/M2 Macrophages and Lymphocytes in Cisplatin-Induced Rat Progressive Renal Fibrosis.
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顺铂诱导的大鼠进行性肾纤维化M1/M2巨噬细胞和淋巴细胞的免疫表型特征
DOI：
10.3390/cells10020257
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发表时间：
2021-01-28
期刊：
影响因子：
6
通讯作者：
Yamate J
中科院分区：
文献类型：
--
作者：
Nakagawa M;Karim MR;Izawa T;Kuwamura M;Yamate J
肾纤维化被认为是导致慢性肾脏疾病的共同最终途径，巨噬细胞和肌成纤维细胞在纤维化的发展中起重要作用。给F344大鼠注射一次顺铂（CDDP; 6 mg/kg BW）治疗肾脏病变。本研究通过组织病理学观察CDDP诱导的大鼠肾脏病变中巨噬细胞和淋巴细胞的免疫表型特征，CDDP诱导的肾脏病变包括早期的组织损害，中期的损害加重并开始间质纤维化，晚期的进行性纤维化; KIM-1表达和α-SMA+肌成纤维细胞面积分别反映肾小管损伤/异常再生和肾间质纤维化。CD 68 + M1巨噬细胞中期开始增多，M1相关细胞因子（INF-γ、TNF-α和IL-6）mRNA表达增加，晚期略有下降。CD 163 + M2巨噬细胞在中晚期逐渐增多，并伴有TGF-β1（一种纤维化因子）mRNA表达增加。使用晚期纤维化样本的双重免疫荧光显示，62.0-78.0%的CD 68 + M1巨噬细胞共表达CD 163，表明M1/M2巨噬细胞可能协同促进进行性肾纤维化;此外，表达MHC II类的巨噬细胞倾向于M1极化，而表达CD 204的巨噬细胞倾向于M2极化。此外，CD 4+和CD 8 + T细胞在晚期增加。总的来说，进行性肾间质纤维化可能是通过M1/M2巨噬细胞（M1的炎症和M2的抗炎）与对CD 4（辅助细胞）和CD 8（细胞毒性）反应的T细胞相互作用产生的复杂机制发展的。本研究为进一步探讨炎症细胞介导的肾纤维化的发病机制提供了依据。
Renal fibrosis is regarded as the common final pathway leading to chronic kidney diseases; macrophages and myofibroblasts play important roles in the development of fibrosis. F344 rats were injected once with cisplatin (CDDP; 6 mg/kg BW) for renal lesions. Here, immunophenotypical characteristics of macrophages and lymphocytes in CDDP-induced rat renal lesions were investigated histopathologically; the CDDP-induced renal lesions consisted of tissue damage at the early-stage, worsen the damage and commencement of interstitial fibrosis at the mid-stage, and progressive fibrosis at the late stage; the KIM-1 expression and α-SMA+ myofibroblast area reflected renal tubular damage/abnormal regeneration and renal interstitial fibrosis, respectively. CD68+ M1 macrophages began to increase at the mid-stage, with increased mRNA expressions of M1-related cytokines (INF-γ, TNF-α and IL-6), and then slightly decreased at the late-stage. CD163+ M2 macrophages showed a gradually increased number at the mid- and late-stages, accompanied by increased TGF-β1 mRNA expression (a fibrogenic factor). Double immunofluorescence using fibrotic samples at the late-stage revealed that 62.0–78.0% of CD68+ M1 macrophages co-expressed CD163, indicating that M1/M2 macrophages may contribute to progressive renal fibrosis in cooperation; further, MHC class II-expressing macrophages had a tendency towards M1 polarization, whereas CD204-expressing macrophages towards M2 polarization. In addition, CD4+ and CD8+ T cells were increased at the late-stage. Collectively, progressive renal interstitial fibrosis may be developed by complicated mechanisms that arose via interaction of M1/M2 macrophages (inflammatory for M1 and anti-inflammatory for M2) and T cells reacting to CD4 (for helper) and CD8 (for cytotoxicity). This study would provide some information on the pathogenesis of renal fibrosis based on inflammatory cells.
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作者：
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通讯作者：
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