Fibrocyte activation in rheumatoid arthritis.
OBJECTIVE
RA is a common, relapsing autoimmune disease primarily affecting the joints. Fibroblast-like synovial (FLS) cells are thought to be responsible for pannus formation and secretion of factors that recruit leucocytes to affected joints, thereby promoting bone and cartilage destruction. Fibrocytes are multipotent circulating stem cells that may have a role in RA pathogenesis, perhaps as the precursors of the FLS cells, or by regulating FLS cell function.


METHODS
We utilized multidimensional phospho-specific flow cytometry to characterize the activation status of peripheral blood (PB) fibrocytes derived from human RA patients at different stages of disease and from mice with CIA.


RESULTS
Human PB fibrocytes from RA patients exhibited phosporylation activation of the p44/42 and p38 MAP kinases (MAPKs), and STAT3 (signal transducer and activator of transcription) and STAT-5 early in disease, within the first year of diagnosis. Similarly, in murine CIA, an increase in the total number of PB phosphoSTAT5-positive fibrocytes was observed at early time points in disease. Notably, in the affected paws of mice with CIA, we identified an increased number of fibrocytes, in contrast to the paws of control mice.


CONCLUSIONS
These data suggest that activated fibrocytes may influence the disease process in RA and may serve as surrogate markers for disease in the PB of affected patients.
Toronto General Research Institute, University Health Network, 67 College Street, 4-424, Toronto, Ontario M5G 2M1, Canada.
Carole L
CL
Galligan
Katherine A
KA
Siminovitch
Edward C
EC
Keystone
Vivian
V
Bykerk
Omar D
OD
Perez
Eleanor N
EN
Fish
D000328:Adult; D000818:Animals; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000276:immunology / Q000378:metabolism*; D002478:Cells, Cultured; D003239:Connective Tissue Cells / Q000276:immunology / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000276:immunology / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D008875:Middle Aged; D015398:Signal Transduction; D013583:Synovial Membrane / Q000166:cytology / Q000276:immunology / Q000378:metabolism