Monocyte extracellular traps: features of generation in rheumatoid arthritis depending on the stage of autoimmune inflammation

Abstract

Recent investigations have demonstrated the involvement of neutrophils and neutrophil extracellular traps (NETs) in the initiation and progression of autoimmune inflammation in rheumatoid arthritis (RA) patients. Simultaneously, macrophages/monocytes, which are the main antigen-presenting cells, play a key role in the immune response as a result of disruption of antigen processing and presentation. Studying the role of monocytes and monocyte extracellular traps (METs) in RA pathogenesis is promising and is of particular interest. The aim of the research was to study the features of the main parameters of monocyte extracellular generation traps in RA patients depending on the stage of autoimmune inflammation. Material and methods. 37 RA patients and 30 healthy individuals were enrolled in study. Circulating monocytes were purified with centrifugation procedure using iohexol with a 1068 kg/m3 density gradient. Cells were identified histochemically, and the extent of monocyte activation was assessed using common nitroblue tetrazolium test. The generation of METs was stimulated by phorbol-12-myristate-13-acetate (PMA), and visualized using fluorescence microscopy with SYBR green. Results and discussion. In patients with inactive RA, the number of monocytes in a state of generating both spontaneous and PMA-induced METs is higher compared to the reference group. The transformation of autoimmune inflammation from remission to the active phase was accompanied by a further increase in the proportion of monocytes that form METs spontaneously and in the presence of PMA (by 114.7 % and 44.2 %, respectively, relative to the comparison group). The growth rate of spontaneous METs formation is 2.6 times higher than induced METs; RA activation is evidenced by an increase in the number of monocytes in the process of spontaneous formation of METs by more than 17.8 %. Conclusions. The obtained data suggest METs participation in the initiation and maintenance of RA autoimmune inflammation along with NETs presumably through exhibition their citrulline neoepitopes. METs could probably be considered as a new potential diagnostic biomarker.

Keywords

• monocytes
• rheumatoid arthritis
• мets
• etosis
• autoimmune inflammation