S100A8/A9 和 S100A12 在 MPO-ANCA 阳性血管炎患者中的潜在致病作用。
The potential pathogenic roles of S100A8/A9 and S100A12 in patients with MPO-ANCA-positive vasculitis.
机构信息
Department of Nephrology, Tianjin Medical University General Hospital, No. 154 Anshan Road, Heping District, Tianjin, 300052, People's Republic of China.
Department of Hematology, Tianjin Medical University General Hospital, No. 154 Anshan Road, Heping District, Tianjin, People's Republic of China.
出版信息
BMC Immunol. 2022 Sep 10;23(1):42. doi: 10.1186/s12865-022-00513-4.
BACKGROUND
The significance of S100A8/A9 and S100A12 in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) has not been clarified. This study was dedicated to exploring the potential pathogenic roles of S100A8/A9 and S100A12 in patients with myeloperoxidase (MPO)-ANCA-positive vasculitis.
METHODS
Serum and urine concentrations of S100A8/A9 and S100A12 of forty-two AAV patients were evaluated. The influence of S100A8/A9 and S100A12 on the chemotaxis, the apoptosis, the release of IL-1β, the complement activation, the respiratory burst, as well as the neutrophil extracellular traps (NETs) formation of MPO-ANCA-activated neutrophils was investigated.
RESULTS
The serum and urine S100A8/A9 and S100A12 of active MPO-AAV significantly increased (compared with inactive AAV and healthy controls, p < 0.001) and were correlated with the severity of the disease. In vitro study showed that S100A8/A9 and S100A12 activated the p38 MAPK/NF-κB p65 pathway, increased the chemotaxis index (CI) and the release of IL-1β, extended the life span, and enhanced the complement activation ability of MPO-ANCA-activated neutrophils. The Blockade of TLR4 and RAGE inhibited the effects of S100A8/A9 and S100A12. All above-mentioned effects of S100A8/A9 and S100A12 were ROS-independent because neither S100A8/A9 nor S100A12 enhanced the ROS formation and NETs formation of MPO-ANCA-activated neutrophils.
CONCLUSION
S100A8/A9 and S100A12 serve as markers for assessing the disease severity, and they may also play a role in MPO-AAV pathogenesis.
背景
S100A8/A9 和 S100A12 在抗中性粒细胞胞质抗体（ANCA）相关性血管炎（AAV）中的意义尚未阐明。本研究旨在探讨 S100A8/A9 和 S100A12 在髓过氧化物酶（MPO）-ANCA 阳性血管炎患者中的潜在致病作用。
方法
评估了 42 例 AAV 患者的血清和尿液中 S100A8/A9 和 S100A12 的浓度。研究了 S100A8/A9 和 S100A12 对 MPO-ANCA 激活的中性粒细胞趋化性、凋亡、IL-1β 释放、补体激活、呼吸爆发以及中性粒细胞胞外陷阱（NETs）形成的影响。
结果
活动期 MPO-AAV 的血清和尿液 S100A8/A9 和 S100A12 显著增加（与非活动期 AAV 和健康对照组相比，p<0.001），并与疾病的严重程度相关。体外研究表明，S100A8/A9 和 S100A12 激活了 p38 MAPK/NF-κB p65 通路，增加了趋化指数（CI）和 IL-1β 的释放，延长了 MPO-ANCA 激活的中性粒细胞的寿命，并增强了补体激活能力。TLR4 和 RAGE 的阻断抑制了 S100A8/A9 和 S100A12 的作用。S100A8/A9 和 S100A12 的所有上述作用均与 ROS 无关，因为 S100A8/A9 和 S100A12 均未增强 MPO-ANCA 激活的中性粒细胞的 ROS 形成和 NETs 形成。
结论
S100A8/A9 和 S100A12 可作为评估疾病严重程度的标志物，它们也可能在 MPO-AAV 的发病机制中发挥作用。
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