Department of Urology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Department of Urology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; Neurology Sub-center, China National Clinical Research Center for Neurologic Diseases, Beijing, China.
Transplant Proc. 2021 Jan-Feb;53(1):436-442. doi: 10.1016/j.transproceed.2020.06.033. Epub 2020 Aug 6.
To investigate the effect and mechanism of macrophage activation and graft damage caused by nucleoside triphosphate diphosphohydrolase 1 (NTPDase1) in acute antibody-mediated rejection (AMR).
Acute AMR was induced in different skin-grafted nude mouse models with wild-type NTPDase1 expression, transgene-enhanced NTPDase1 expression, or NTPDase1 gene knockout. Several methods (eg, real-time fluorescence quantitative polymerase chain reaction, high-performance liquid chromatography [HPLC], immunofluorescence, flow cytometry, and luciferin/luciferase assays) were used to study (at the histologic and molecular levels) the extracellular adenosine diphosphate (ADP) concentration, macrophage proliferation, major histocompatibility complex (MHC) class II antigen expression on the surface of macrophages, B-cell activating factor (BAFF) expression in the peripheral blood serum, and the total number of SmIg-positive B cells during acute AMR. The relative activity of NTPDase1 in B cells and epithelial cells, pathologic changes, and the incidence of positive C4d deposition around the capillaries of skin grafts on the different nude mice were studied.
Macrophages proliferated significantly when acute AMR occurred. The higher the NTPDase1 expression level, the lower the extracellular ADP concentration, the expression of MHC class II antigens on the surface of macrophages, the expression of BAFF in the peripheral blood serum, and the total number of SmIg-positive B cells, indicating negative correlations. The relative activity of NTPDase1 in B cells and epithelial cells of the skin graft was different among the different mice. The higher the NTPDase1 expression level, the lower the degree of pathologic damage to the skin graft.
Imbalance in extracellular ADP degradation by NTPDase1 may promote macrophage activation, and activated macrophages may be an important cause of graft damage.
研究核苷酸三磷酸二磷酸水解酶 1（NTPDase1）介导的巨噬细胞激活和移植物损伤在急性抗体介导排斥反应（AMR）中的作用及机制。
在具有野生型 NTPDase1 表达、转基因增强型 NTPDase1 表达或 NTPDase1 基因敲除的不同皮肤移植裸鼠模型中诱导急性 AMR。采用实时荧光定量聚合酶链反应、高效液相色谱（HPLC）、免疫荧光、流式细胞术和荧光素/荧光素酶测定等方法（如实时荧光定量聚合酶链反应、高效液相色谱、免疫荧光、流式细胞术和荧光素/荧光素酶测定）研究（在组织学和分子水平上）细胞外二磷酸腺苷（ADP）浓度、巨噬细胞增殖、巨噬细胞表面主要组织相容性复合体（MHC）Ⅱ类抗原表达、外周血血清中 B 细胞激活因子（BAFF）表达以及急性 AMR 时 SmIg 阳性 B 细胞总数。研究不同裸鼠皮肤移植物 B 细胞和上皮细胞中 NTPDase1 的相对活性、病理变化以及皮肤移植物毛细血管周围 C4d 沉积的阳性率。
急性 AMR 时巨噬细胞明显增殖。NTPDase1 表达水平越高，细胞外 ADP 浓度越低，巨噬细胞表面 MHC Ⅱ类抗原表达越低，外周血血清中 BAFF 表达越低，SmIg 阳性 B 细胞总数越低，呈负相关。不同裸鼠皮肤移植物中 B 细胞和上皮细胞中 NTPDase1 的相对活性不同。NTPDase1 表达水平越高，皮肤移植物的病理损伤程度越低。
NTPDase1 降解细胞外 ADP 的失衡可能促进巨噬细胞的激活，而激活的巨噬细胞可能是移植物损伤的重要原因。
