Ohara Y, Yabuki A, Nakamura R, Ichii O, Mizukawa H, Yokoyama N, Yamato O
Laboratory of Veterinary Clinical Pathology, Joint Faculty of Veterinary Medicine, Kagoshima University, Kagoshima.
Laboratory of Veterinary Clinical Pathology, Joint Faculty of Veterinary Medicine, Kagoshima University, Kagoshima.
J Comp Pathol. 2019 Jul;170:53-59. doi: 10.1016/j.jcpa.2019.05.006. Epub 2019 Jun 18.
During the progression of chronic kidney disease (CKD), macrophage infiltration is a crucial event leading to tubulointerstitial fibrosis. In the present study, macrophages infiltrating renal tissue in dogs and cats with CKD were analysed immunohistochemically. Iba-1 was used as a pan-macrophage marker, CD204 was used as a marker of M2 macrophages and tumour necrosis factor (TNF)-α was used as a marker of M1 macrophages. Signals for Iba1 and CD204 were observed in the interstitium of all tested kidney samples. In dogs, the signals were diffusely scattered. In cats, both diffuse and focal signals were observed. Cells that were positive for Iba1 and CD204 were also observed in the tubular lumina in cats. Co-expression of Iba1 and CD204 was also observed in the infiltrating cells by immunofluorescence labelling, and these cells were negative for TNF-α. By quantitative analysis, the indices for Iba1- and CD204-positive cells were significantly correlated with the concentrations of plasma creatinine and/or urea and the extent of interstitial fibrosis in both dogs and cats. These results demonstrated that renal infiltration of M2 macrophages plays an important role in the progression of CKD in dogs and cats. The distribution pattern of the kidney-infiltrating macrophages was unique in cats and may be associated with a cat-specific renal fibrotic process.
在慢性肾脏病(CKD)进展过程中,巨噬细胞浸润是导致肾小管间质纤维化的关键事件。在本研究中,对患有CKD的犬猫肾组织中浸润的巨噬细胞进行了免疫组织化学分析。Iba-1用作全巨噬细胞标志物,CD204用作M2巨噬细胞标志物,肿瘤坏死因子(TNF)-α用作M1巨噬细胞标志物。在所有测试的肾脏样本间质中均观察到Iba1和CD204信号。在犬中,信号呈弥漫性散在分布。在猫中,观察到弥漫性和局灶性信号。在猫的肾小管腔中也观察到Iba1和CD204阳性的细胞。通过免疫荧光标记在浸润细胞中也观察到Iba1和CD204的共表达,并且这些细胞TNF-α呈阴性。通过定量分析,Iba1和CD204阳性细胞指数与犬猫的血浆肌酐和/或尿素浓度以及间质纤维化程度显著相关。这些结果表明,M2巨噬细胞的肾浸润在犬猫CKD进展中起重要作用。肾脏浸润巨噬细胞的分布模式在猫中是独特的,可能与猫特异性肾纤维化过程有关。