Expression of chemokines and matrix metalloproteinases in early rheumatoid arthritis.
OBJECTIVE
To compare macrophage infiltration and expression of chemokines and matrix metalloproteinases (MMPs) in synovial tissue between patients with early and long-standing rheumatoid arthritis (RA).


METHODS
Knee synovial biopsies were taken from 22 patients with early (<1 yr) and 22 patients with long-standing (>5 yr) RA and immunostained with antibodies specific for CD68; macrophage inflammatory protein (MIP)-1alpha and monocyte chemoattractant protein (MCP)-1; MMP-1 and -3 and the tissue inhibitors of metalloproteinases (TIMP)-l and -2. Immunostaining was quantified using a colour video image analysis system.


RESULTS
CD68+ macrophage infiltration and the expression of MIP-1alpha, MCP-1, MMP-1, MMP-3, TIMP-1, and TIMP-2 were observed in synovial tissue of patients with early RA. In long-standing RA, there was a further increase in CD68+ macrophage infiltration and MIP-1alpha expression in the synovial lining layer. CD68 expression correlated with MIP-1alpha (R=0.39, P=0.01), but not with MCP-1 expression.


CONCLUSIONS
Macrophage accumulation, and the expression of chemokines and MMPs in synovial tissue occur in early RA. Targeting chemokines which play a role in the migration of macrophages into the joints may be of therapeutic benefit in RA patients.
Katrib
A
A
Rheumatology Unit, Prince of Wales Hospital, Inflammation Research Unit, School of Pathology, University of New South Wales, Sydney, Australia.
Tak
P P
PP
Bertouch
J V
JV
Cuello
C
C
McNeil
H P
HP
Smeets
T J
TJ
Kraan
M C
MC
Youssef
P P
PP
D000368:Aged; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D001172:Arthritis, Rheumatoid / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D018925:Chemokines / Q000378:metabolism*; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007124:Immunoenzyme Techniques; D007596:Joints / Q000473:pathology / Q000503:physiopathology; D007719:Knee Joint / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D012720:Severity of Illness Index; D013583:Synovial Membrane / Q000378:metabolism / Q000473:pathology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D018925:Chemokines; D020782:Matrix Metalloproteinases; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; C067980:CD68 antigen, human; D000097382:CD68 Molecule