Advances in Clinical and Experimental Medicine
2015, vol. 24, nr 5, September-October, p. 807–813
doi: 10.17219/acem/27302
Publication type: original article
Language: English
Download citation:
Fibroblast-Like Synovial Cells in Rheumatoid Arthritis – the Impact of Infliximab on Hexosaminidase Activity
1 Department of Orthopedics and Traumatology, Bialystok Hospital, Poland
2 Department of Otolaryngology, Medical University of Bialystok, Poland
3 Department of Pediatric Orthopedics, Medical University of Bialystok, Poland
4 Department of Cytogenetics, Medical University of Bialystok, Poland
5 Department of Rheumatology and Internal Diseases, Medical University of Bialystok, Poland
6 Medical College of the Universal Education Society, Łomża, Poland
Abstract
Background. The effect of multiple infusions of infliximab (INF), a chimeric anti-tumor necrosis factor alpha antibody, on the concentration of hexosaminidase (HEX) activity in a synovial cell culture derived from human synovial inflamed fluid obtained from patients suffering from rheumatoid arthritis (RA) has been evaluated.
Objectives. The aim of this study was to prove INF efficacy in RA.
Material and Methods. Inflamed synovial fluid was taken from RA patients (a study group) and patients who had undergone knee trauma within 7 days (a control group). The following solutions of infliximab were used: 40, 60 and 140 μg/mL. Determination of the concentration of HEX activity in cell cultures was performed after 24, 48, 72 and 96 h of infliximab administration. To identify synoviocytes in cell culture immunohistochemical staining with vimentin and pancytokeratin was performed.
Results. A predominance of fibroblast-like synovial cells has been observed in the study group. In the control group the concentration of HEX activity without adding infliximab to the cell culture was 283.00 nkat/mL. After 96 h of incubation with infliximab, the concentrations of HEX activity in cultured synoviocytes according to infliximab doses of 40, 60 and 140 μg/mL were respectively: 280.00, 271.50 and 293.50 nkat/mL. In the study group, the concentration of HEX activity without adding infliximab to the cell culture was 542.27 nkat/mL. The final concentrations of HEX activity of cultured fibroblast-like synovial cells measured after 96 h of incubation with infliximab were: 471.72, 498.27 and 556.72 nkat/mL, according to infliximab doses of 40, 60 and 140 μg/mL. In all groups (besides the infliximab concentration of 140 μg/mL after 96 h of incubation), the level of concentration of HEX activity was significantly higher in the study group compared to the control group, irrespective of infliximab concentration and time of infliximab incubation.
Conclusion. Infliximab changes the concentration of HEX activity depending on the drug dose and time of administration.
Key words
infliximab, inflamed synovial fluid, fibroblasts in vitro, hexosaminidase activity
References (25)
- Smolen JS, Steiner G: Therapeutic strategies for rheumatoid arthritis. Nat Rev Drug Discov 2003, 2, 473–488.
- Redlich K, Hayer S, Ricci R, David JP, Tohidast-Akrad M, Kollias G, Steiner G, Smolen JS, Wagner EF, Schett G: Osteoclasts are essential for TNF-α-mediated joint destruction. J Clin Invest 2002, 110, 1419–1427.
- Choy EH, Panayi GS: Cytokines pathways and joint inflammation in rheumatoid arthritis. N Eng J Med 2001, 344, 907–916.
- Chojnowska S, Kepka A, Szajda SD, Waszkiewicz N, Bierc M, Zwierz K: Exoglycosidase markers of diseases. Biochem Soc Trans 2011, 39, 406–409.
- Elliott MJ, Maini RN, Feldmann M, Kalden JR, Antoni C, Smolen JS, Leeb B, Breedveld FC, Macfarlane JD, Bijl H: Randomised double-blind comparison of chimeric monoclonal antibody to tumour necrosis factor alpha (cA2) versus placebo in rheumatoid arthritis. Lancet 1994, 344, 1105–1110.
- Smeets TJ, Kraan MC, van Loon ME, Tak PP: Tumor necrosis factor alpha blockade, but apparently not by induction of apoptosis in synovial tissue. Arthritis Rheum 2003, 48, 2155–2162.
- Zwierz K, Zalewska A, Zoch-Zwierz W: Isoenzymes of N-acetyl-β-hexosaminidase. Acta Biochim Pol 1999, 46, 739–751.
- Rye CS, Withers SG: Glycosidase mechanisms. Curr Opin Chem Biol 2000, 4, 573–580.
- Lerner UH: Transforming growth factor-β stimulates bone resorption in neonatal mouse calvariae by a prostaglandinunrelated but cell proliferation-dependent pathway. J Bone Miner Res 1996, 11, 1628–1639.
- Faid V, Evjen G, Tollersrud OK, Michalski JC, Morelle W: Site-specific glycosylation analysis of the bovine lysosomal alpha-mannosidase. Glycobiology 2006, 16, 440–461.
- Perry W: Rifampicin, halothane and glucose as mediators of lysosomal enzyme release and tissue damage. Med Hypotheses 1988, 26, 131–134.
- Casal JA, Mera A, Pérez LF, Tutor JC: Plasma and peripheral leukocyte beta-N-acetylhexosaminidase isoenzymes and disease activity in rheumatoid arthritis. Clin Biochem 2002, 35, 483–488.
- Pásztói M, Sódar B, Misják P, Pálóczi K, Kittel Á, Tóth K, Wellinger K, Géher P, Nagy G, Lakatos T, Falus A, Buzás EI: The recently identified hexosaminidase D enzyme substantially contributes to the elevated hexosaminidase activity in rheumatoid arthritis. Immunol Lett 2013, 149, 71–76.
- Pásztói M, Nagy G, Géher P, Lakatos T, Tóth K, Wellinger K, Pócza P, György B, Holub MC, Kittel A, Pálóczy K, Mazán M, Nyirkos P, Falus A, Buzas EI: Gene expression and activity of cartilage degrading glycosidases in human rheumatoid arthritis and osteoarthritis synovial fibroblasts. Arthitis Res Ther 2009, 11, R6 8.
- Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, Healey LA, Kaplan SR, Liang MH, Luthra HS: The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 1988, 31, 315–324.
- Zwierz K, Gindzienski A, Glowacka D, Porowski T: The degradation of glycoconjugates in the human gastric mucous membrane. Acta Med Acad Sci Hung 1981, 38, 145–152.
- Pancewicz S, Popko J, Rutkowski R, Knas M, Grygorczuk S, Guszczyn T, Bruczko M, Szajda S, Zajkowska J, Kondrusik M, Sierakowski S, Zwierz K: Activity of lysosomal exoglycosidases in serum and synovial fluid in patients with chronic Lyme and rheumatoid arthritis. Scand J Infect Dis 2009, 41, 584–589.
- Akimoto R, Pawankar R, Yagi T, Baba S: Acquired and congenital cholesteatoma: determination of tumor necrosis factor-alpha intercellular adhesion molecule-1, interleukin-1-alpha and lymphocyte functional antigen-1 in the inflammatory process. ORL J Otorhinolaryngol Relat Spec 2000, 62, 257–265.
- Schatteman L, Gyselbrecht L, De Clercq L, Mielants H: Treatment of refractory inflammatory monoarthritis in ankylosing spondylitis by intraarticular injection of infliximab. J Rheumatol 2006, 33, 82–85.
- Tse SM, Burgos-Vargas R, Laxer RM: Anti-tumor necrosis factor alpha blockade in the treatment of juvenile spondylarthropathy. Arthritis Rheum 2005, 52, 2103–2108.
- Van der Bijl AE, Goekoop-Ruiterman YP, de Vries-Bouwstra JK, Ten Wolde S, Han KH, van Krugten MV, Allaart CF, Breedveld FC, Dijkmans BA: Infliximab and methotrexate as induction therapy in patients with early rheumatoid arthritis. Arthritis Rheum 2007, 56, 2129–2134.
- Van der Bijl AE, Teng YK, van Oosterhout M, Breedveld FC, Allaart CF, Huizinga TW: Efficacy of intraarticular infliximab in patients with chronic or recurrent gonarthritis: a clinical randomized trial. Arthritis Rheum 2009, 61, 974–978.
- Vastesaeger N, Xu S, Aletaha D, St Clair EW, Smolen JS: A pilot risk model for the prediction of rapid radiographic progression in rheumatoid arthritis. Rheumatology (Oxford) 2009, 48, 1114–1121.
- Klimiuk PA, Sierakowski S, Domyslawska I, Chwiecko J: Regulation of serum chemokines following infliximab therapy in patients with rheumatoid arthritis. Clin Exp Rheumatol 2006, 24, 529–533.
- Fisher BA, Keat A: Should we be using intraarticular tumor necrosis factor blockade in inflammatory monoarthritis? J Rheumatol 2006, 33, 1934–1935.


