148539 20250125205839.0 doi 10.1016/j.joca.2017.06.007 sideral 99596 ART-2017-99596 eng Jaime, P. Universidad de Zaragoza (orcid)0000-0002-8731-4269 CD56+/CD16- Natural Killer cells expressing the inflammatory protease granzyme A are enriched in synovial fluid from patients with osteoarthritis 2017 Access copy available to the general public Unrestricted Objective: Natural killer (NK) cells have been involved in the pathology of different inflammatory and autoimmune disorders. Inflammation is an important regulator of osteoarthritis (OA), but the molecular and cellular mechanisms regulating this process are not well defined. Design To understand the role of NK cells in OA, we have compared the phenotype (CD56 subsets and perforin and granzyme expression) and cytotoxic function of NK cells in peripheral blood and synovial fluid from patients with OA undergoing total knee arthroplasty. Results: In contrast to peripheral blood lymphocytes (PBLs), the majority of NK cells from the synovial fluid were CD56brightCD16(-) cells. As expected the expression of the cytolytic mediators perforin and granzyme B in CD56brightCD16(-) cells was low and correlated with a poor cytotoxic potential against K562 sensitive target cells. Surprisingly, this low cytotoxic NK cell subset expressed high levels of granzyme A (a protease recently characterized as a key modulator of inflammation in mouse models) in synovial fluid but not in peripheral blood. The presence of the CD56(+)brightCD16(-) cells expressing granzyme A correlated with increased levels of pro-inflammatory cytokines in synovial fluid from OA patients. Conclusion: Our results indicate that NK cells from the synovium of patients with OA, which present an immunoregulatory non-cytotoxic phenotype, show different phenotype comparing with NK cells from peripheral blood, especially expressing granzyme A, a pro-inflammatory molecule which may contribute to the establishment of chronic articular inflammation in this type of patients. info:eu-repo/grantAgreement/ES/DGA-FSE/B27 info:eu-repo/grantAgreement/ES/MINECO-FEDER/SAF2011-25390 info:eu-repo/grantAgreement/ES/MINECO/SAF2014-54763-C2-1-R info:eu-repo/grantAgreement/EUR/TRAIN2/SOE2-P1-E-341 info:eu-repo/semantics/openAccess by-nc-nd http://creativecommons.org/licenses/by-nc-nd/3.0/es/ 5.454 2017 RHEUMATOLOGY 4 / 30 = 0.133 2017 Q1 T1 ORTHOPEDICS 2 / 77 = 0.026 2017 Q1 T1 2.497 2017 Biomedical Engineering 2017 Q1 Rheumatology 2017 Q1 Orthopedics and Sports Medicine 2017 Q1 info:eu-repo/semantics/article info:eu-repo/semantics/acceptedVersion García-Guerrero, N. Universidad de Zaragoza Estella, R. Pardo, J. Universidad de Zaragoza (orcid)0000-0003-0154-0730 García-Álvarez, F. Universidad de Zaragoza (orcid)0000-0003-2587-7506 Martínez-Lostao, L. Universidad de Zaragoza (orcid)0000-0003-3043-147X 1008 566 Universidad de Zaragoza Dpto. Microb.Med.Pr.,Sal.Públ. Área Inmunología 1004 830 Universidad de Zaragoza Dpto. Cirugía,Ginecol.Obstetr. Área Traumatología y Ortopedia 1002 060 Universidad de Zaragoza Dpto. Bioq.Biolog.Mol. Celular Área Bioquímica y Biolog.Mole. 25, 10 (2017), 1708-1718 Osteoarthr. cartil. Osteoarthritis and cartilage 1063-4584 559592 http://zaguan.unizar.es/record/148539/files/texto_completo.pdf Postprint 1471966 http://zaguan.unizar.es/record/148539/files/texto_completo.jpg?subformat=icon icon Postprint oai:zaguan.unizar.es:148539 articulos driver 2025-01-25-20:57:57 ARTICLE