Non-inflammatory macrophages phagocytose and hydrolyse monosodium urate crystals in different stages of gout

Objective: 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. Method: 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. Results: 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. Conclusion: 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.