Huang Y-J, Wang L-C, Wang C-P, Yu K-H, Kuo C-F
School of Medicine, Chang Gung University, Taoyuan, Taiwan.
Division of Rheumatology, Allergy and Immunology, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
Scand J Rheumatol. 2025 Jul;54(4):292-301. doi: 10.1080/03009742.2025.2491176. Epub 2025 May 8.
Macrophages play a crucial role in gouty arthritis; however, the relationship between non-inflammatory macrophages (M0) and different stages of gout remains unclear. This study aimed to investigate the phagocytosis, hydrolysis, and subsequent cytokine secretion of monosodium urate (MSU) by non-inflammatory macrophages in patients in different stages of gout.
Non-inflammatory macrophages were derived from monocytes through stimulation with macrophage colony-stimulating factor (M-CSF) for a duration of 10 days. The study included patients with asymptomatic hyperuricaemia, intercritical gout, tophaceous gout, and a normal control group. The phagocytic and hydrolytic capabilities of non-inflammatory macrophages were measured using flow cytometry based on the increase in side-scatter area. In addition, to evaluate the relationship between the hydrolysis capability of non-inflammatory macrophages and subsequent inflammation, we cultured them with lipopolysaccharide (LPS) and/or MSU.
We discovered that M0 macrophages were capable of phagocytosing and hydrolysing MSU crystals in various stages of gout, including the control group. Patients with asymptomatic hyperuricaemia exhibited the most pronounced phagocytic and hydrolytic capabilities, surpassing even those of the normal control group. The presence of MSU alone did not induce the secretion of pro-inflammatory cytokines. However, in experiments where M0 macrophages were stimulated with LPS and/or MSU, the phagocytic and hydrolytic abilities of M0 macrophages were correlated with inflammatory cytokine elevation.
The efficient phagocytosis and hydrolysis of MSU crystals by M0 macrophages suggest their role in maintaining the non-inflammatory stage of gout. Our findings suggest that non-inflammatory macrophages play a role in gout.
巨噬细胞在痛风性关节炎中起关键作用;然而,非炎性巨噬细胞(M0)与痛风不同阶段之间的关系尚不清楚。本研究旨在调查痛风不同阶段患者的非炎性巨噬细胞对尿酸单钠(MSU)的吞噬、水解及随后的细胞因子分泌情况。
通过巨噬细胞集落刺激因子(M-CSF)刺激单核细胞10天来获得非炎性巨噬细胞。该研究纳入无症状高尿酸血症患者、发作间期痛风患者、痛风石性痛风患者以及一个正常对照组。基于侧向散射面积的增加,使用流式细胞术测量非炎性巨噬细胞的吞噬和水解能力。此外,为了评估非炎性巨噬细胞的水解能力与随后炎症之间的关系,我们用脂多糖(LPS)和/或MSU对其进行培养。
我们发现M0巨噬细胞能够在痛风的各个阶段(包括对照组)吞噬和水解MSU晶体。无症状高尿酸血症患者表现出最显著的吞噬和水解能力,甚至超过正常对照组。单独存在MSU并不会诱导促炎细胞因子的分泌。然而,在M0巨噬细胞用LPS和/或MSU刺激的实验中,M0巨噬细胞的吞噬和水解能力与炎性细胞因子升高相关。
M0巨噬细胞对MSU晶体的有效吞噬和水解表明它们在维持痛风非炎性阶段中发挥作用。我们的研究结果表明非炎性巨噬细胞在痛风中起作用。