Practical Journal of Organ Transplantation(Electronic Version) ›› 2022, Vol. 10 ›› Issue (4): 320-325.DOI: 10.3969/j.issn.2095-5332.2022.04.006

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Analysis of different subtypes of macrophages infiltrated in kidney allografts with antibody mediated rejection 

Deng Ge1，Dou Meng1，Gong Huilin2，Zheng Bingxuan1，Shi Yuting1，Wei Tian1，Ding Chenguang1，Zheng Jin1，Ding Xiaoming1，Xue Wujun1，Tian Puxun1.   

  1. 1. Department of Kidney Transplantation，Nephropathy Hospital，the First Affiliated Hospital of Xi'an Jiaotong University，Xi’an 710061，Shaanxi，China；

    2. Department of Pathology，the First Affiliated Hospital of Xi'an Jiaotong University，Xi’an 710061，Shaanxi，China

  • Online:2022-07-20 Published:2022-09-01

肾移植术后抗体介导排斥反应中不同亚型的巨噬细胞浸润分析

邓格 1 ，豆猛 1 ，宫惠琳 2 ，郑秉暄 1 ，石玉婷 1 ，卫田 1 ，丁晨光 1 ，郑瑾 1 ，丁小明 1 ，薛武军 1，田普训 1   

  1. 1. 西安交通大学第一附属医院肾脏病医院肾移植科，陕西 西安 710061 ；

    2. 西安交通大学第一附属医院病理科，陕西 西安 710061

  • 基金资助:

    国家自然科学基金（81870514；81670681） 

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Abstract:

Objective To discuss the expression and scientific significance of different subtypes of macrophages in antibody-mediated rejection（ABMR）after kidney transplantation. Methods The CIBERSORT algorithm was performed to analyze immune cells infiltration in GEO dataset GSE36059. There were three groups of renal biopsies，normal kidneys as the Control group，renal allografts with Stable renal function as the stable group and the ABMR group. After fixed with 4% paraformaldehyde，embedded in paraffin and sectionalized，these tissues were stained using immunohistochemistry（IHC）to observe the positive degree and location of markers CD31，CD68，CD86 and CD206. In combination with relevant clinical data，the correlation between the infiltration of different subtypes of macrophages and renal function were analyzed. Results The analysis of GSE36059 showed that the percentage of macrophages M0 and macrophages M1 were significantly increased in ABMR group compared with Stable group. IHC staining showed that the number of macrophages infiltrated in the ABMR group was significantly increased compared with Control group and Stable group，and the infiltrated macrophages were mainly distributed around the microvessels （glomerulus and interstitial capillaries）. Further classification of the infiltrated macrophages in the ABMR group showed that there were mainly macrophages M1 while macrophages M2 was not significant. The infiltration degree of macrophages and macrophages M1 in the glomerular was significantly correlated with renal function（correlation coefficients were 0.795 and 0.823，respectively）. Conclusion When ABMR occurred in renal allografts，macrophages M1 were mainly infiltrated and located around microvessels. We hypothesized that endothelial cells of microvessels can recruit chemotactic macrophages，and the macrophage-endothelial interaction may be involved in the pathogenesis of ABMR. 

Key words:

Kidney transplantation, Antibody mediated rejection, Macrophage, Endothelial cell

摘要：

目的 探讨不同亚型巨噬细胞在肾移植抗体介导排斥反应（antibody-mediated rejection，ABMR）中的表达和科学意义。方法 利用 CIBERSORT 算法对 GEO 数据集 GSE36059 中的免疫细胞浸润进行分析。选取三组肾脏穿刺组织，分为正常肾脏组（Control 组）、移植肾肾功能稳定组（Stable 组）、ABMR组。组织经 4% 多聚甲醛溶液固定、石蜡包埋、切片后，进行免疫组化染色，观察 CD31、CD68、CD86、CD206 的染色程度及阳性部位。结合相关临床资料，分析巨噬细胞及其亚型的浸润程度与肾功能的相关性。结果 GSE36059 分析显示，与 Stable 组相比，ABMR 组浸润的 M0 巨噬细胞和 M1 型巨噬细胞显著增多。免疫组化染色结果显示，与 Control 组和 Stable 组相比，ABMR 组的移植肾内浸润的总巨噬细胞数量明显增多，其主要分布在微血管周围（肾小球内和间质毛细血管）。对 ABMR 组中浸润的巨噬细胞进一步分型表明，以 M1 型巨噬细胞为主，M2 型巨噬细胞浸润不显著。肾小球内总巨噬细胞及 M1 型巨噬细胞浸润程度与移植肾功能显著相关（相关系数分别为 0.795 和 0.823）。 结论 肾移植受者发生 ABMR 时，M1 型巨噬细胞显著浸润，且主要浸润在移植肾组织内的微血管周围。我们推测微血管的内皮细胞可以招募趋化巨噬细胞，而巨噬细胞 - 内皮细胞的相互作用可能参与了 ABMR 的发生。

关键词:

肾移植 , 抗体介导排斥反应 , 巨噬细胞 , 内皮细胞

Practical Journal of Organ Transplantation(Electronic Version)
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