Neutrophil extracellular traps release in gout and pseudogout depends on the number of crystals regardless of leukocyte count
| Autor: | Orso-Maria Lucherini, Bruno Frediani, Enrico Selvi, Sergio Tripodi, Alessandra Alì, Antonella Simpatico, Sauro Lorenzini, Pietro Enea Lazzerini, Estrella Garcia-Gonzalez, Alessandra Gamberucci |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Pathology medicine.medical_specialty Gout Neutrophils Necroptosis medicine.medical_treatment Blotting Western Arthritis Chondrocalcinosis Extracellular Traps microcrystals 03 medical and health sciences Leukocyte Count 0302 clinical medicine pseudogout Rheumatology medicine Synovial fluid Humans Pharmacology (medical) crystal-induced arthritis 030203 arthritis & rheumatology business.industry Elastase Arthrocentesis neutrophil extracellular traps (NETs) Neutrophil extracellular traps medicine.disease Flow Cytometry 030104 developmental biology Case-Control Studies Pseudogout business gout |
| Zdroj: | Rheumatology (Oxford, England). 60(10) |
| ISSN: | 1462-0332 |
| Popis: | Objectives Microcrystal-induced arthritis is still an unresolved paradigm for medicine. Overt inflammation may be absent even when crystals occur in SF. Recently, the production of neutrophil extracellular traps (NETs) embedding MSU crystals has been proposed as a possible mechanism of the auto-resolution of the inflammatory phase during gout. We aimed to verify and quantify the release of NETs in SFs during gout and pseudogout attacks and to compare any differences with respect to crystals and neutrophils number, and to analyse activation of necroptosis pathway in SF from crystal-induced arthritis. Methods SF samples were obtained by arthrocentesis from 22 patients presenting acute crystal-induced arthritis, gout or pseudogout (n = 11 each group), and from 10 patients with acute non-crystal arthritis as controls. NETosis was quantified in SF by nucleic acid stain and by quantification of human neutrophil elastase. Activation of phosphorylated MLKL was assessed by western blot. Results We observed that SF neutrophils encountering MSU and CPPD crystals during episodes of gout and pseudogout release NETs in relation to the number of crystals in SF and irrespective of neutrophil density and type of crystal. This release was accompanied by necroptosis through the activation of the MLKL pathway. Conclusions Our findings suggest that a role of NETs in crystal-induced arthritis is to ‘trap extracellular particles’, including microcrystals. Embedding crystals in aggregates of NETs may be the basis of tophi and CPPD deposition, and may have implications for disease evolution rather than for spontaneous resolution of the acute attack. |
| Databáze: | OpenAIRE |
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