CD56+/CD16− Natural Killer cells expressing the inflammatory protease granzyme A are enriched in synovial fluid from patients with osteoarthritis

Jaime, P.; Garcia-Guerrero, N.; Estella, R.; Pardo, Julián; García-Álvarez, F; Martínez-Lostao, Luis

doi:10.1016/j.joca.2017.06.007

Cited by 45 publications

(32 citation statements)

References 36 publications

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“…Using mouse models, we show that NK cells are the major source of mGzmA, consistent with other studies in mice (33,85). CD56+ NK cells have also been described in CHIKV patients (46,47) and human CD56 hi NK cells have been shown to express high levels of hGzmA, with relatively low levels of perforin (19,86). NK cells are part of the early innate anti-viral response to many virus infections (65), consistent with the early rise in serum hGzmA and mGzmA described herein.…”

Section: Discussionsupporting

confidence: 76%

“…Although GzmA often remains classified as a cytotoxic mediator (7,9,10), an emerging paradigm is that the primary physiological role of GzmA is promotion of inflammation in a variety of settings (11)(12)(13)(14)(15). GzmA has, for instance, been implicated as an important proinflammatory mediator in inter alia rheumatoid arthritis (16,17), psoriasis (18), and osteoarthritis (19). A number of mechanisms have been proposed whereby GzmA might mediate this activity, including intracellular cleavage of pro-IL-1β (20) or SET complex proteins (21,22), and/or extracellular cleavage of pro-urokinase (23) or protease activated receptors 1 and 2 (PAR-1 and PAR-2) (24)(25)(26)(27) or potentiation of TLR2/4 (28) and/or TLR9 (29) signaling, with the latter two potentially not requiring GzmA's protease activity.…”

Section: Introductionmentioning

confidence: 99%

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Granzyme A in Chikungunya and Other Arboviral Infections

Soares‐Schanoski

Kaiserman

et al. 2020

Front. Immunol.

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Granzyme A (GzmA) is secreted by cytotoxic lymphocytes and has traditionally been viewed as a mediator of cell death. However, a growing body of data suggests the physiological role of GzmA is promotion of inflammation. Here, we show that GzmA is significantly elevated in the sera of chikungunya virus (CHIKV) patients and that GzmA levels correlated with viral loads and disease scores in these patients. Serum GzmA levels were also elevated in CHIKV mouse models, with NK cells the likely source. Infection of mice deficient in type I interferon responses with CHIKV, Zika virus, or dengue virus resulted in high levels of circulating GzmA. We also show that subcutaneous injection of enzymically active recombinant mouse GzmA was able to mediate inflammation, both locally at the injection site as well as at a distant site. Protease activated receptors (PARs) may represent targets for GzmA, and we show that treatment with PAR antagonist ameliorated GzmA-and CHIKV-mediated inflammation.

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Section: Discussionsupporting

confidence: 76%

Section: Introductionmentioning

confidence: 99%

Granzyme A in Chikungunya and Other Arboviral Infections

Soares‐Schanoski

Kaiserman

et al. 2020

Front. Immunol.

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“…Thus, in an experimental mouse model of CHIKV infection, extension of oedema was correlated with high NK activity, whereas the depletion of NK cells significantly reduced acute joint pathology, thus corroborating the deleterious role of NK cells in driving virus-induced pathology [61]. These data are consistent with those obtained in degenerative joint disease associated with osteoarthritis in which synovial tissue-infiltrating NK cells displayed impaired IFN-γ production, suggesting that NK cells contribute to the evolution of disease [62,63].…”

Section: Nk Cell Responses Following Arbovirus Infectionsupporting

confidence: 74%

Control of Acute Arboviral Infection by Natural Killer Cells

Maucourant

Petitdemange

Yssel

et al. 2019

Viruses

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The recent explosive pandemic of chikungunya virus (CHIKV) followed by Zika (ZIKV) virus infections occurring throughout many countries represents the most unexpected arrival of arthropod-borne viral diseases in the past 20 years. Transmitted through the bite of Aedes mosquitoes, the clinical picture associated with these acute arbovirus infections, including Dengue (DENV), CHIKV and ZIKV, ranges from classical febrile illness to life-threatening disease. Whereas ZIKV and CHIKV-mediated infections have previously been recognized as relatively benign diseases, in contrast to Dengue fever, recent epidemic events have brought waves of increased morbidity and mortality leading to a serious public health problem. Although the host immune response plays a crucial role in controlling infections, it may also promote viral spread and immunopathology. Here, we review recent developments in our understanding of the immune response, with an emphasis on the early antiviral immune response mediated by natural killer cells and emphasize their Janus-faced effects in the control of arbovirus infection and pathogenesis. Improving our understanding knowledge on of the mechanisms that control viral infection is crucial in the current race against the globalization of arbovirus epidemics.

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“…In contrast to peripheral NK cells, the NK cells from synovial fluid expressed different phenotypes, with considerable potential to produce pro-inflammatory molecules, especially granzyme A, a proinflammatory molecule recently identified in animal studies. 18 …”

Section: Discussionmentioning

confidence: 99%

Is there a relationship between the neutrophil/lymphocyte ratio and bilaterality in patients with coxarthrosis?

Barbosa

Vicente

Fagundes

et al. 2018

Revista Brasileira de Ortopedia (English Edition)

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ObjectiveThe objective of this study was to evaluate the relationship between the neutrophil/lymphocyte ratio and the presence of signs of arthrosis in both hips in patients followed at this medical center.MethodsThis was a cross-sectional, retrospective study through the analysis of medical records and database review of patients over 18 years of age with hip arthrosis, followed at the outpatient clinic of this hospital.ResultsRegarding the analysis of the Mann–Whitney test to correlate the neutrophil/lymphocyte ratio and laterality, a bi-lateral test result of p = 0.036 was obtained, thus demonstrating a significant difference between the observed groups. When we analyzed the absolute values of neutrophils and lymphocytes, the authors obtained results of p = 0.14 and p = 0.24. Therefore, it was not possible to observe statistically significant differences between the absolute values in the two groups.ConclusionConsidering the interactions between the inflammatory mechanisms in osteoarthritis and the fact that the interaction between neutrophils and lymphocytes has differences in relation to the laterality of the coxarthrosis, it is hypothesized that the inflammatory etiology of unilateral and bilateral osteoarthritis could have different dynamics. However, more in-depth studies with flow cytometry are needed to assess the possible impact of these differences in the inflammatory mechanisms observed in this study.

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CD56+/CD16− Natural Killer cells expressing the inflammatory protease granzyme A are enriched in synovial fluid from patients with osteoarthritis

Cited by 45 publications

References 36 publications

Granzyme A in Chikungunya and Other Arboviral Infections

Granzyme A in Chikungunya and Other Arboviral Infections

Control of Acute Arboviral Infection by Natural Killer Cells

Is there a relationship between the neutrophil/lymphocyte ratio and bilaterality in patients with coxarthrosis?

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