Session Type: Abstract Submissions (ACR)
The central role of the monocyte-macrophage system in gout has been highlighted during the last years. Macrophages initiate the inflammatory response to monosodium urate (MSU) crystals and produce inflammatory cytokines and chemokines that induce migration of blood monocytes to further amplify the inflammatory response. Different subpopulations of blood monocytes have been recognised: classical (CD14++CD16-), intermediate (CD14++CD16+) and non-classical (CD14+CD16++); characteristically intermediate monocytes are expanded in infectious and inflammatory diseases. One of the questions that remain unanswered is why some patients with hyperuricemia, and even with MSU deposits, remain clinically asymptomatic. We investigated the possibility that it could be due to a greater inflammasome reactivity to MSU crystals in patients who develop gout. Moreover, we analyzed the distribution of monocyte subpopulations in patients with gout.
Seventeen patients with gout were selected, 13 asymptomatic and in 4 patients samples were obtained during an acute flare. Nineteen healthy donors were selected for comparison. Inflammasome activity was assessed by the increase of active caspase-1 after stimulation with MSU in peripheral blood mononuclear cells (PBMCs) by flow cytometry using Caspase-1 FLICA™ Detection Kit (Immunochemistry Technologies). Phagocytosis of MSU crystals was quantified by flow cytometry, as cells that phagocyte crystals increase their side scatter (SSC) values. PBMCs were cultured for 24 hours in the presence of MSU (200 µg/ml), LPS (100 ng/ml) or both and IL-1β was quantified by ELISA. Samples of peripheral blood were stained with CD45, HLA-DR, CD16, and CD14 antibodies and analyzed by flow cytometry. Uric acid, creatinine and C-reactive protein (CRP) were quantified in sera. Flow cytometry and statistics analysis were performed with the FACSDiva and GraphPad Prism 5 respectively.
No differences were observed in active caspase-1 at baseline between patients and controls. However, when stimulated with MSU, monocytes from gout patients exhibited a higher increase of active caspase-1 (mean+/-SEM, gout 2.20+/-0.15, controls 1.66+/-0.18, p= 0.0419). Differences in phagocytosis of MSU crystals were excluded, as in both groups monocytes exhibited equivalent phagocytic capability. PBMCs of patients with gout exhibited diminished IL-1β production when challenged with LPS and MSU (p=0.0473). Regarding monocyte subpopulations, the intermediate phenotype was expanded in patients with gout during an acute flare and a weak correlation between intermediate monocytes and CRP was observed.
Monocytes of patients with gout exhibited an enhanced inflammasome activation with MSU crystals, suggesting that the reduced threshold in the inflammatory response could be involved in the development of clinical gout. The expansion of intermediate monocytes was observed during gout flares and, although it cannot be excluded that intermediate monocytes could be “innocent bystanders” in the context of inflammation, it could suggest that these monocytes participate in the inflammatory response to MSU crystals.
E. A. Gonzalez-Navarro,
F. X. Alemany,
« Back to 2014 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-monocyte-phagocyte-system-in-gout-enhanced-inflammasome-activity-and-expansion-of-cd14cd16-monocytes-in-patients-with-gout/