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反复注射顺铂后大鼠肾纤维化中出现的巨噬细胞和淋巴细胞的特性。

Properties of macrophages and lymphocytes appearing in rat renal fibrosis followed by repeated injection of cisplatin.

机构信息

Laboratory of Veterinary Pathology, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, 1-58 Rinku-Ourai-Kita, Izumisano-shi, Osaka 598-8531, Japan.

Department of Pathology, Faculty of Veterinary Science, Bangladesh Agricultural University, Mymensingh-2202, Bangladesh.

出版信息

J Vet Med Sci. 2021 Sep 15;83(9):1435-1442. doi: 10.1292/jvms.21-0341. Epub 2021 Jul 22.

DOI:10.1292/jvms.21-0341
PMID:34305076
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8498843/
Abstract

Properties of macrophages and lymphocytes appearing in renal fibrosis remains to be investigated. F344 rats were injected once a week with cisplatin (2 mg/kg body weight) for 8 weeks and examined at post-final injection weeks 1, 3, 6, 9, and 12. Rats developed progressive renal fibrosis at weeks 1 to 6 as fibrosis-progress phase, and subsequent amelioration at weeks 9 and 12. CD68 M1-macrophages and major histocompatibility complex (MHC) class II macrophages remarkably increased persistently, whereas CD163 M2-macrophages slightly increased. MHC class II/CD68 and MHC class II/CD163 macrophages were present, indicating that MHC class II macrophages might have both functions of M1- and M2-macrophages. In the fibrosis-progress phase, interleukin (IL)-6, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ for M1-factors, and transforming growth factor (TGF)-β1 and IL-10 for M2-factors tended to increase; tissue injury by M1 and fibrosis by M2 might have occurred simultaneously. Lots of CD4 and CD8 T cells appeared in close relation with MHC class II macrophages, and mainly CD4 T cells formed aggregations. In the lymphocyte aggregates collected by laser microdissection, expression of IL-17A (for Th17 cells) and forkhead box P3 (FoxP3) (for Treg) significantly increased at weeks 1 and 6, respectively; presumably, Th17 cells might be involved in tissue injury, whereas Treg might be related to fibrosis amelioration. These results suggested that macrophages and T cells may contribute interrelatedly to renal fibrosis.

摘要

在肾纤维化中出现的巨噬细胞和淋巴细胞的特性仍有待研究。F344 大鼠每周接受一次顺铂(2mg/kg 体重)注射,共 8 周,并在最后一次注射后的第 1、3、6、9 和 12 周进行检查。在第 1 至 6 周的纤维化进展阶段,大鼠逐渐发生进行性肾纤维化,随后在第 9 和 12 周得到改善。CD68 M1 型巨噬细胞和主要组织相容性复合体(MHC)II 型巨噬细胞显著持续增加,而 CD163 M2 型巨噬细胞略有增加。MHC II/CD68 和 MHC II/CD163 巨噬细胞存在,表明 MHC II 型巨噬细胞可能具有 M1 和 M2 巨噬细胞的双重功能。在纤维化进展阶段,M1 因子的白细胞介素(IL)-6、肿瘤坏死因子(TNF)-α 和干扰素(IFN)-γ,以及 M2 因子的转化生长因子(TGF)-β1 和 IL-10 倾向于增加;M1 的组织损伤和 M2 的纤维化可能同时发生。大量的 CD4 和 CD8 T 细胞与 MHC II 型巨噬细胞密切相关,并主要由 CD4 T 细胞形成聚集。在通过激光微切割收集的淋巴细胞聚集物中,IL-17A(Th17 细胞)和叉头框 P3(FoxP3)(Treg)的表达分别在第 1 和 6 周显著增加;推测 Th17 细胞可能参与组织损伤,而 Treg 可能与纤维化改善有关。这些结果表明,巨噬细胞和 T 细胞可能相互作用参与肾纤维化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05d3/8498843/76559041a8ff/jvms-83-1435-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05d3/8498843/75faff39f04f/jvms-83-1435-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05d3/8498843/62818f0a37ac/jvms-83-1435-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05d3/8498843/f58953c6091e/jvms-83-1435-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05d3/8498843/76559041a8ff/jvms-83-1435-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05d3/8498843/75faff39f04f/jvms-83-1435-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05d3/8498843/62818f0a37ac/jvms-83-1435-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05d3/8498843/f58953c6091e/jvms-83-1435-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05d3/8498843/76559041a8ff/jvms-83-1435-g004.jpg

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Toxicol Pathol. 2021 Jul;49(5):1048-1061. doi: 10.1177/0192623320982526. Epub 2021 Jan 5.
3
Acetaminophen-Induced Rat Hepatotoxicity Based on M1/M2-Macrophage Polarization, in Possible Relation to Damage-Associated Molecular Patterns and Autophagy.
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T Cells in Fibrosis and Fibrotic Diseases.T 细胞与纤维化及纤维性疾病
Front Immunol. 2020 Jun 26;11:1142. doi: 10.3389/fimmu.2020.01142. eCollection 2020.
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