Skewed balance in basal expression and regulation of activating v inhibitory Fcgamma receptors in macrophages of collagen induced arthritis sensitive mice.
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.
Blom
A B
AB
Department of Rheumatology, University Medical Centre St Radboud, Nijmegen, The Netherlands. a.blom@reuma.umcn.nl
van Lent
P L E M
PL
Holthuysen
A E M
AE
Jacobs
C
C
van den Berg
W B
WB
D000818:Animals; D000936:Antigen-Antibody Complex / Q000276:immunology*; D001169:Arthritis, Experimental / Q000276:immunology*; D024043:Collagen Type II / Q000276:immunology*; D017364:Collagenases / Q000096:biosynthesis; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry / Q000379:methods; D006614:Hindlimb; D007150:Immunohistochemistry / Q000379:methods; D007375:Interleukin-1 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D008264:Macrophages / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D010529:Peritoneal Cavity; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017452:Receptors, IgG / Q000032:analysis*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013583:Synovial Membrane / Q000276:immunology
D000936:Antigen-Antibody Complex; D024043:Collagen Type II; D007375:Interleukin-1; D015850:Interleukin-6; D012333:RNA, Messenger; D017452:Receptors, IgG; D017364:Collagenases