Skewed balance in basal expression and regulation of activating v inhibitory Fcgamma receptors in macrophages of collagen induced arthritis sensitive mice.
SourceAnnals of the Rheumatic Diseases, 62, 5, (2003), pp. 465-471
Article / Letter to editor
Display more detailsDisplay less details
Annals of the Rheumatic Diseases
SubjectUMCN 1.4: Immunotherapy, gene therapy and transplantation; UMCN 4.2: Chronic inflammation and autoimmunity; UMCN 4.3: Tissue engineering and reconstructive surgery; UMCN 5.4: Renal disorders
BACKGROUND: Recently, it has been found that collagen type II arthritis susceptible mouse strains are hyperreactive to immune complexes (ICs), locally deposited into their knee joints. OBJECTIVE: To investigate whether this strain specific knee joint hyperreactivity is related to a disturbed regulation of activatory and inhibitory FcgammaR on their macrophages before and after stimulation with ICs. METHODS: Macrophages from collagen induced arthritis susceptible strains (DBA/1 and B10.RIII) and non-susceptible strains (C57BL/6 and BALB/c) were compared. FcgammaR levels on macrophages were detected at protein level by flow cytometric analysis and at mRNA level by reverse transcriptase-polymerase chain reaction. Macrophages were stimulated with ICs, and production of cytokines and enzymes was measured at different times. RESULTS: On synovial and peritoneal macrophages of DBA/1 mice a higher basal FcgammaRII and III expression was found, which was skewed towards the activating FcgammaRIII. In B10.RIII macrophages, however, FcgammaRIII levels were much lower. Regulation of FcgammaR mRNA levels in macrophages was tested after stimulation with ICs for one and three days. DBA/1 and B10.RIII macrophages showed a prolonged up regulation of activating FcgammaRI and III, whereas the inhibiting FcgammaRII was significantly down regulated compared with non-susceptible strains. In line with this, DBA/1 and B10.RIII macrophages showed a higher interleukin 1 (IL1) and matrix metalloproteinase (MMP) production after IC exposure, whereas IL6 production was significantly reduced. CONCLUSIONS: This study indicates that macrophages derived from collagen type II arthritis susceptible mice show a disregulated FcgammaR expression before, and even more clearly, after activation by ICs involved in inflammation and cartilage degradation, resulting in prolonged expression of activatory FcgammaRI and III, down regulation of inhibitory FcgammaRII and increased release of IL1 and MMP.
Upload full text
Use your RU credentials (u/z-number and password) to log in with SURFconext to upload a file for processing by the repository team.