Department of Nephrology, Xiangya Hospital, Central South University, Changsha, China.
Center of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, China.
Front Immunol. 2022 Aug 19;13:929244. doi: 10.3389/fimmu.2022.929244. eCollection 2022.
Monocytes are involved in the pathogenesis of ANCA-associated vasculitis (AAV). Monocyte/macrophages are the dominant infiltrating cells in the glomeruli of patients with myeloperoxidase-AAV (MPO-AAV). However, how human monocyte subsets extravasate to the kidney in MPO-AAV with renal damage is unclear.
30 MPO-AAV patients with renal damage and 22 healthy controls were enrolled in this study. Monocyte subsets and monocyte-related chemokines in the blood and kidneys of MPO-AAV patients were detected. The chemoattractant activity of the CX3CL1-CX3CR1 axis on CD16 monocytes was observed. The effect of MPO-ANCA on the migration of CD16 monocytes to human glomerular endothelial cells (HGECs) was detected by flow cytometry and transwell migration assay.
Compared with controls, CD16 monocytes were significantly decreased in the blood and increased in the glomeruli of MPO-AAV patients with renal damage. The level of CX3CL1, but not CCL2, was significantly increased in the plasma of MPO-AAV patients. CX3CL1 co-localized with glomerular endothelial cells in MPO-AAV patients with renal damage. Moreover, we initially found that MPO-ANCA promotes an increase of the chemokine CX3CL1 on HGECs, imposing recruitment on CD16 monocytes. Finally, the percentage of CD16 monocytes in the blood was found to be positively correlated with estimated glomerular filtration rate (eGFR) and negatively correlated with urinary protein creatinine ratio in MPO-AAV patients with renal damage. Furthermore, the urinary protein creatinine ratio was positively correlated with the infiltrating of CD14 and CD16 cells in the kidneys.
Enhanced extravasation of CD16 monocytes to the kidney the CX3CL1-CX3CR1 axis may be involved in renal damage in MPO-AAV.
单核细胞参与抗中性粒细胞胞浆抗体（ANCA）相关性血管炎（AAV）的发病机制。单核细胞/巨噬细胞是髓过氧化物酶-AAV（MPO-AAV）患者肾小球中主要浸润细胞。然而，在伴有肾损伤的 MPO-AAV 中，人单核细胞亚群如何渗出到肾脏尚不清楚。
本研究纳入了 30 例伴有肾损伤的 MPO-AAV 患者和 22 名健康对照者。检测 MPO-AAV 患者血液和肾脏中的单核细胞亚群和单核细胞相关趋化因子。观察 CX3CL1-CX3CR1 轴对 CD16 单核细胞的趋化活性。通过流式细胞术和 Transwell 迁移实验检测 MPO-ANCA 对 CD16 单核细胞向人肾小球内皮细胞（HGECs）迁移的影响。
与对照组相比，伴有肾损伤的 MPO-AAV 患者血液中的 CD16 单核细胞明显减少，而肾小球中 CD16 单核细胞明显增多。MPO-AAV 患者血浆中 CX3CL1 水平明显升高，而 CCL2 水平无明显升高。CX3CL1 在伴有肾损伤的 MPO-AAV 患者的肾小球内皮细胞中存在共定位。此外，我们首次发现 MPO-ANCA 可促进 HGECs 上趋化因子 CX3CL1 的增加，从而导致 CD16 单核细胞的募集。最后，我们发现伴有肾损伤的 MPO-AAV 患者血液中 CD16 单核细胞的百分比与估算肾小球滤过率（eGFR）呈正相关，与尿蛋白肌酐比呈负相关。此外，尿蛋白肌酐比与肾脏中 CD14 和 CD16 细胞的浸润呈正相关。
增强 CD16 单核细胞向肾脏的渗出，以及 CX3CL1-CX3CR1 轴可能参与了 MPO-AAV 的肾损伤。
