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Skewed balance in basal expression and regulation of activating v inhibitory Fcγ receptors in macrophages of collagen induced arthritis sensitive mice
  1. A B Blom1,
  2. P L E M van Lent1,
  3. A E M Holthuysen1,
  4. C Jacobs2,
  5. W B van den Berg1
  1. 1Department of Rheumatology, University Medical Centre St Radboud, Nijmegen, The Netherlands
  2. 2Department of Nephrology, University Medical Centre St Radboud, Nijmegen, The Netherlands
  1. Correspondence to:
    Dr A B Blom, Department of Rheumatology, University Medical Centre St Radboud, Geert Groote plein 26–28, 6500 HB Nijmegen, The Netherlands;
    a.blom{at}reuma.umcn.nl

Abstract

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 FcγR 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. FcγR 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 FcγRII and III expression was found, which was skewed towards the activating FcγRIII. In B10.RIII macrophages, however, FcγRIII levels were much lower. Regulation of FcγR 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 FcγRI and III, whereas the inhibiting FcγRII 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 FcγR expression before, and even more clearly, after activation by ICs involved in inflammation and cartilage degradation, resulting in prolonged expression of activatory FcγRI and III, down regulation of inhibitory FcγRII and increased release of IL1 and MMP.

  • mouse CD16
  • mouse CD32
  • arthritis
  • cytokines
  • enzymes
  • APMA, p-aminophenylmercuric acetate
  • CIA, collagen induced arthritis
  • DMEM, Dulbecco’s modified Eagle’s medium
  • ELISA, enzyme linked immunosorbent assay
  • FCS, fetal calf serum
  • GAPDH, glyceraldehyde-3-phosphate dehydrogenase
  • HAGG, heat aggregated gammaglobulins
  • IC, immune complex
  • IL, interleukin
  • MHC, major histocompatibility complex
  • MMP, matrix metalloproteinase
  • RA, rheumatoid arthritis
  • RT-PCR, reverse transcriptase-polymerase chain reaction

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