Overexpression of heparanase enhances T lymphocyte activities and intensifies the inflammatory response in a model of murine rheumatoid arthritis

Digre, Andreas,1987-Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Jin-Ping Li (författare)

Heparanase is an endo-glucuronidase that degrades heparan sulfate chains. The enzyme is expressed at a low level in normal organs; however, elevated expression of heparanase has been detected in several inflammatory conditions, e.g. in the synovial joints of rheumatoid arthritis (RA) patients. Herein, we have applied the model of collagen-induced arthritis (CIA) to transgenic mice overexpressing human heparanase (Hpa-tg) along with wildtype (WT) mice. About 50 % of the induced animals developed clinical symptoms, i.e. swelling of joints, and there were no differences between the Hpa-tg and WT mice in the incidence of disease. However, Hpa-tg mice displayed an earlier response and developed more severe symptoms. Examination of cells from thymus, spleen and lymph nodes revealed increased innate and adaptive immune responses of the Hpa-tg mice, reflected by increased proportions of macrophages, antigen presenting cells and plasmacytoid dendritic cells as well as Helios-positive CD4+ and CD8+ T cells. Furthermore, splenic lymphocytes from Hpa-tg mice showed higher proliferation activity. Our results suggest that elevated expression of heparanase augmented both the innate and adaptive immune system and propagated inflammatory reactions in the murine RA model.

Singh, KailashUppsala universitet,Institutionen för medicinsk cellbiologi,Stellan Sandler(Swepub:uu)kaisi212 (författare)
Åbrink, MagnusSwedish University of Agricultural Sciences,Sveriges lantbruksuniversitet,Inst för biomedicin och veterinär folkhälsovetenskap,Department of Biomedical Science and Veterinary Public Health,Swedish Univ Agr Sci, Immunol Sect, Dept Biomed Sci & Vet Publ Hlth, VHC, Box 7028, Uppsala, Sweden(Swepub:slu)48145 (författare)
Reijmers, Rogier M.Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands (författare)
Sandler, StellanUppsala universitet,Institutionen för medicinsk cellbiologi,Stellan Sandler(Swepub:uu)stelsand (författare)
Vlodavsky, IsraelCancer and Vascular Biology Research Center, The Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel,Israel Vlodavsky (författare)
Li, Jin-PingUppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Jin-Ping Li(Swepub:uu)jinpili (författare)
Uppsala universitetInstitutionen för medicinsk biokemi och mikrobiologi (creator_code:org_t)
Sveriges lantbruksuniversitet

Av författaren/redakt...: Digre, Andreas, ...; Singh, Kailash; Åbrink, Magnus; Reijmers, Rogier ...; Sandler, Stellan; Vlodavsky, Israe ...; visa fler...; Li, Jin-Ping; visa färre...

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