Advertisement

Phenotypic and functional characterisation of synovial fluid-derived neutrophils in knee osteoarthritis and knee infection

Published:October 06, 2022DOI:https://doi.org/10.1016/j.joca.2022.09.011

      Summary

      Objective

      An increase in the number of neutrophils (NEUs) has long been associated with infections in the knee joints; however, their impact on knee osteoarthritis (KOA) pathophysiology remains largely unexplored.

      Design

      This study compared the phenotypic and functional characteristics of synovial fluid (SF)-derived NEUs in KOA and knee infection (INF).

      Results

      KOA NEUs were characterised by a lower expression of CD11b, CD54, and CD64 and higher expression of CD62L, TLR2, and TLR4 compared with INF NEUs. Except for CCL2, lower levels of inflammatory mediators and proteases were detected in KOA SF than in INF SF. Functionally, KOA NEUs displayed increased reactive oxygen species production and phagocytic activity compared with INF NEUs. Moreover, KOA and INF NEUs differed in cell sizes, histological characteristics of the surrounding synovial tissues, and their effects on the endothelial cells assessed by human umbilical vein endothelial cells. When KOA patients were subdivided based on the SF NEU abundance, patients with high NEUs (10%–60%) were characterised by i) elevated SF protein levels of TNF-α, IL-1RA, MMP-9, sTREM-1, VILIP-1 and ii) lower CD54, CD64, TLR2 and TLR4 expression compared to patients with low NEUs (<10%). Analysis of paired SF samples suggests that low or high NEU percentages, respectively, persist throughout the course of disease.

      Conclusions

      Our findings suggest that NEU may play a significant role in KOA pathophysiology. Further studies should explore the mechanisms that contribute to the increased number of NEUs in SF and the clinical consequences of neutrophilic phenotype in KOA.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Osteoarthritis and Cartilage
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Woodell-May J.E.
        • Sommerfeld S.D.
        Role of inflammation and the immune system in the progression of osteoarthritis.
        J Orthop Res. 2020; 38: 253-257
        • Jiang Y.
        Osteoarthritis year in review 2021: biology.
        Osteoarthr Cartil. 2022; 30: 207-215
        • Felson D.T.
        • Niu J.
        • Neogi T.
        • Goggins J.
        • Nevitt M.C.
        • Roemer F.
        • et al.
        Synovitis and the risk of knee osteoarthritis: the MOST Study.
        Osteoarthr Cartil. 2016; 24: 458-464
        • Batushansky A.
        • Zhu S.
        • Komaravolu R.K.
        • South S.
        • Mehta-D'souza P.
        • Griffin T.M.
        Fundamentals of OA. An initiative of osteoarthritis and cartilage. Chapter 9: obesity and metabolic factors in OA.
        Osteoarthr Cartil. 2022; 30: 501-515
        • Sokolove J.
        • Lepus C.M.
        Role of inflammation in the pathogenesis of osteoarthritis: latest findings and interpretations.
        Ther Adv Musculoskelet Dis. 2013; 5: 77-94
        • Kulkarni P.
        • Martson A.
        • Vidya R.
        • Chitnavis S.
        • Harsulkar A.
        Pathophysiological landscape of osteoarthritis.
        Adv Clin Chem. 2021; 100: 37-90
        • Wang X.
        • Hunter D.
        • Xu J.
        • Ding C.
        Metabolic triggered inflammation in osteoarthritis.
        Osteoarthr Cartil. 2015; 23: 22-30
        • Livshits G.
        • Kalinkovich A.
        Hierarchical, imbalanced pro-inflammatory cytokine networks govern the pathogenesis of chronic arthropathies.
        Osteoarthr Cartil. 2018; 26: 7-17
        • Boff D.
        • Crijns H.
        • Teixeira M.M.
        • Amaral F.A.
        • Proost P.
        Neutrophils: beneficial and harmful cells in septic arthritis.
        Int J Mol Sci. 2018; 19: 468
        • Hsueh M.F.
        • Zhang X.
        • Wellman S.S.
        • Bolognesi M.P.
        • Kraus V.B.
        Synergistic roles of macrophages and neutrophils in osteoarthritis progression.
        Arthritis Rheumatol. 2021; 73: 89-99
        • Kriegova E.
        • Manukyan G.
        • Mikulkova Z.
        • Gabcova G.
        • Kudelka M.
        • Gajdos P.
        • et al.
        Gender-related differences observed among immune cells in synovial fluid in knee osteoarthritis.
        Osteoarthr Cartil. 2018; 26: 1247-1256
        • Wang G.
        • Jing W.
        • Bi Y.
        • Li Y.
        • Ma L.
        • Yang H.
        • et al.
        Neutrophil elastase induces chondrocyte apoptosis and facilitates the occurrence of osteoarthritis via caspase signaling pathway.
        Front Pharmacol. 2021; 12666162
        • Troeberg L.
        • Nagase H.
        Proteases involved in cartilage matrix degradation in osteoarthritis.
        Biochim Biophys Acta. 2012; 1824: 133-145
        • van Lent P.L.
        • Blom A.B.
        • Schelbergen R.F.
        • Sloetjes A.
        • Lafeber F.P.
        • Lems W.F.
        • et al.
        Active involvement of alarmins S100A8 and S100A9 in the regulation of synovial activation and joint destruction during mouse and human osteoarthritis.
        Arthritis Rheum. 2012; 64: 1466-1476
        • Shen H.
        • Kreisel D.
        • Goldstein D.R.
        Processes of sterile inflammation.
        J Immunol. 2013; 191: 2857-2863
        • Lambert C.
        • Zappia J.
        • Sanchez C.
        • Florin A.
        • Dubuc J.E.
        • Henrotin Y.
        The damage-associated molecular patterns (DAMPs) as potential targets to treat osteoarthritis: perspectives from a review of the literature.
        Front Med (Lausanne). 2020; 7607186
        • Zhang W.
        • Doherty M.
        • Peat G.
        • Bierma-Zeinstra M.A.
        • Arden N.K.
        • Bresnihan B.
        • et al.
        EULAR evidence-based recommendations for the diagnosis of knee osteoarthritis.
        Ann Rheum Dis. 2010; 69: 483-489
        • Kellgren J.H.
        • Lawrence J.S.
        Radiological assessment of osteo-arthrosis.
        Ann Rheum Dis. 1957; 16: 494-502
        • MacWilliams P.S.
        • Friedrichs K.R.
        Laboratory evaluation and interpretation of synovial fluid.
        Vet Clin North Am Small Anim Pract. 2003; 33: 153-178
        • Crampton S.P.
        • Davis J.
        • Hughes C.C.
        Isolation of human umbilical vein endothelial cells (HUVEC).
        J Vis Exp. 2007; : 183
        • Tomankova T.
        • Kriegova E.
        • Fillerova R.
        • Luzna P.
        • Ehrmann J.
        • Gallo J.
        Comparison of periprosthetic tissues in knee and hip joints: differential expression of CCL3 and DC-STAMP in total knee and hip arthroplasty and similar cytokine profiles in primary knee and hip osteoarthritis.
        Osteoarthr Cartil. 2014; 22: 1851-1860
        • Krenn V.
        • Morawietz L.
        • Häupl T.
        • Neidel J.
        • Petersen I.
        • König A.
        Grading of chronic synovitis--a histopathological grading system for molecular and diagnostic pathology.
        Pathol Res Pract. 2002; 198: 317-325
        • Loeuille D.
        • Chary-Valckenaere I.
        • Champigneulle J.
        • Rat A.C.
        • Toussaint F.
        • Pinzano-Watrin A.
        • et al.
        Macroscopic and microscopic features of synovial membrane inflammation in the osteoarthritic knee: correlating magnetic resonance imaging findings with disease severity.
        Arthritis Rheum. 2005; 52: 3492-3501
        • Liu-Bryan R.
        • Terkeltaub R.
        Chondrocyte innate immune myeloid differentiation factor 88-dependent signaling drives procatabolic effects of the endogenous Toll-like receptor 2/Toll-like receptor 4 ligands low molecular weight hyaluronan and high mobility group box chromosomal protein 1 in mice.
        Arthritis Rheum. 2010; 62: 2004-2012
        • Mortaz E.
        • Alipoor S.D.
        • Adcock I.M.
        • Mumby S.
        • Koenderman L.
        Update on neutrophil function in severe inflammation.
        Front Immunol. 2018; 9: 2171
        • Sethi S.
        • Chakraborty T.
        Role of TLR-/NLR-signaling and the associated cytokines involved in recruitment of neutrophils in murine models of Staphylococcus aureus infection.
        Virulence. 2011; 2: 316-328
        • Rodriguez B.V.
        • Kuehn M.J.
        Staphylococcus aureus secretes immunomodulatory RNA and DNA via membrane vesicles.
        Sci Rep. 2020; 1018293
        • Dal Ponte S.T.
        • Alegretti A.P.
        • Pilger D.A.
        • Rezende G.P.
        • Andrioli G.
        • Ludwig H.C.
        • et al.
        Diagnostic accuracy of CD64 for sepsis in emergency department.
        J Glob Infect Dis. 2018; 10: 42-46
        • Björnsdottir H.
        • Welin A.
        • Michaëlsson E.
        • Osla V.
        • Berg S.
        • Christenson K.
        • et al.
        Neutrophil NET formation is regulated from the inside by myeloperoxidase-processed reactive oxygen species.
        Free Radic Biol Med. 2015; 89: 1024-1035
        • Song W.
        • Ye J.
        • Pan N.
        • Tan C.
        • Herrmann M.
        Neutrophil extracellular traps tied to rheumatoid arthritis: points to ponder.
        Front Immunol. 2021; 11578129
        • Sauce D.
        • Dong Y.
        • Campillo-Gimenez L.
        • Casulli S.
        • Bayard C.
        • Autran B.
        • et al.
        Reduced oxidative burst by primed neutrophils in the elderly individuals is associated with increased levels of the CD16bright/CD62Ldim immunosuppressive subset.
        J Gerontol A Biol Sci Med Sci. 2017; 72: 163-172
        • Shen X.
        • Cao K.
        • Zhao Y.
        • Du J.
        Targeting neutrophils in sepsis: from mechanism to translation.
        Front Pharmacol. 2021; 12644270
        • Bhan C.
        • Dipankar P.
        • Chakraborty P.
        • Sarangi P.P.
        Role of cellular events in the pathophysiology of sepsis.
        Inflamm Res. 2016; 65: 853-868
        • Pinheiro da Silva F.
        • Aloulou M.
        • Skurnik D.
        • Benhamou M.
        • Andremont A.
        • Velasco I.T.
        • et al.
        CD16 promotes Escherichia coli sepsis through an FcR gamma inhibitory pathway that prevents phagocytosis and facilitates inflammation.
        Nat Med. 2007; 13: 1368-1374
        • Van Avondt K.
        • van Sorge N.M.
        • Meyaard L.
        Bacterial immune evasion through manipulation of host inhibitory immune signaling.
        PLoS Pathog. 2015; 11e1004644
        • Nagao M.
        • Hamilton J.L.
        • Kc R.
        • Berendsen A.D.
        • Duan X.
        • Cheong C.W.
        • et al.
        Vascular endothelial growth factor in cartilage development and osteoarthritis.
        Sci Rep. 2017; 713027
        • Wang L.
        • Luqmani R.
        • Udalova I.A.
        The role of neutrophils in rheumatic disease-associated vascular inflammation.
        Nat Rev Rheumatol. 2022; 18: 158-170
        • Miyake M.
        • Goodison S.
        • Urquidi V.
        • Gomes Giacoia E.
        • Rosser C.J.
        Expression of CXCL1 in human endothelial cells induces angiogenesis through the CXCR2 receptor and the ERK1/2 and EGF pathways.
        Lab Invest. 2013; 93: 768-778
        • Dolzani P.
        • Manferdini C.
        • Meliconi R.
        • Lisignoli G.
        • Pulsatelli L.
        Preliminary study on immune cells in the synovium of end-stage osteoarthritis and rheumatoid arthritis patients: neutrophils and IgG4-secreting plasma cells as differential diagnosis candidates.
        Acta Histochem. 2022; 124151909
        • Li M.
        • Yin H.
        • Yan Z.
        • Li H.
        • Wu J.
        • Wang Y.
        • et al.
        The immune microenvironment in cartilage injury and repair.
        Acta Biomater. 2022; 140: 23-42
        • Henrotin Y.
        • Pesesse L.
        • Lambert C.
        Targeting the synovial angiogenesis as a novel treatment approach to osteoarthritis.
        Ther Adv Musculoskelet Dis. 2014; 6: 20-34