AI Article Synopsis
- The study investigates how integrin CD11b affects inflammasome activation in macrophages when triggered by monosodium urate (MSU) crystals, which are related to gout.
- Researchers used bone marrow-derived macrophages from both wild-type and CD11b knock-out mice to analyze inflammation and metabolic changes caused by MSU.
- Results showed that CD11b-deficient mice experienced more severe symptoms of gouty arthritis, higher levels of inflammatory cytokine IL-1β, and altered macrophage metabolism, suggesting CD11b as a target for potential gout treatments.
Article Abstract
Objective: In gout, monosodium urate crystals are taken up by macrophages, triggering the activation of the NLRP3 inflammasome and the maturation of IL-1β. This study aimed to investigate the role of integrin CD11b in inflammasome activation in macrophages stimulated by MSU.
Methods: BMDM from WT and CD11b KO mice were stimulated in vitro with MSU crystals. Cellular supernatants were collected to assess the expression of the inflammatory cytokines by enzyme-linked immunosorbent assay and western blot methods. The role of integrin CD11b in MSU-induced gouty arthritis in vivo was investigated by intra-articular injection of MSU crystals. Real-time extracellular acidification rate and oxygen consumption rate of BMDMs were measured by Seahorse Extracellular Flux Analyzer.
Results: We demonstrate that CD11b-deficient mice developed exacerbated gouty arthritis with increased recruitment of leukocytes in the joint and higher IL-1β levels in the sera. In macrophages, genetic deletion of CD11b induced a shift of macrophage metabolism from oxidative phosphorylation to glycolysis, thus decreasing the overall generation of intracellular ATP. Upon MSU stimulation, CD11b-deficient macrophages showed an exacerbated secretion of IL-1β. Treating wild-type macrophages with a CD11b agonist, LA1, inhibited MSU-induced release of IL-1β in vitro and attenuated the severity of experimental gouty arthritis. Importantly, LA1, was also effective in human cells as it inhibited MSU-induced release of IL-1β by peripheral blood mononuclear cells from healthy donors.
Conclusion: Our data identified the CD11b integrin as a principal cell membrane receptor that modulates NLRP3 inflammasome activation by MSU crystal in macrophages, which could be a potential therapeutic target to treat gouty arthritis in human patients.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11165854 | PMC |
| http://dx.doi.org/10.1186/s13075-024-03350-5 | DOI Listing |
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