Fractalkine, a novel chemokine in rheumatoid arthritis and in rat adjuvant-induced arthritis.
OBJECTIVE
To examine the expression of the novel CX3C chemokine fractalkine (Fkn) and its receptor (CX3CR1) in rheumatoid arthritis (RA) and rat adjuvant-induced arthritis (AIA), a model of RA.


METHODS
Immunohistochemistry, flow cytometry, enzyme-linked immunosorbent assay (ELISA), reverse transcriptase-polymerase chain reaction (RT-PCR), and chemotaxis assays were used.


RESULTS
In rat AIA, synovial tissue (ST) macrophages, fibroblasts, endothelial cells, and dendritic cells were Fkn immunopositive, whereas lymphocytes did not significantly express Fkn. Significant staining for CX3CR1 was found in ST macrophages, fibroblasts, and dendritic cells, whereas only a small percentage of endothelial cells stained for CX3CR1 in rat AIA. We immunolocalized Fkn to RA ST macrophages, fibroblasts, endothelial cells, and dendritic cells. We also found intense ST macrophage and dendritic cell staining for CX3CR1 in RA ST. Flow cytometry analysis of RA synovial fluid (SF) and peripheral blood revealed a greater percentage of monocytes expressing Fkn and CX3CR1 compared with T cells. By ELISA, we found significantly elevated soluble Fkn (sFkn) levels in RA SF compared with SF from patients with osteoarthritis or other forms of arthritis. By RT-PCR, we found enhanced expression of Fkn and CX3CR1 mRNA on day 18 in rat AIA, a time of pronounced inflammation in the rat joint. Soluble Fkn-depleted RA SF showed significantly decreased chemotactic activity for monocytes compared with sham-depleted RA SF.


CONCLUSIONS
These results indicate that Fkn and its receptor are both expressed in RA and in rat AIA, and that sFkn is up-regulated in RA SF. Furthermore, our data suggest a new role for Fkn in monocyte chemotaxis in the inflamed RA joint.
Ruth
J H
JH
Northwestern University Medical School, Chicago, Illinois 60611, USA.
Volin
M V
MV
Haines
G K
GK
Woodruff
D C
DC
Katschke
K J
KJ
Woods
J M
JM
Park
C C
CC
Morel
J C
JC
Koch
A E
AE
D000328:Adult; D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology / Q000378:metabolism*; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000378:metabolism*; D017252:CD3 Complex / Q000032:analysis; D000073883:CX3C Chemokine Receptor 1; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C / Q000032:analysis / Q000235:genetics*; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005434:Flow Cytometry; D015870:Gene Expression / Q000276:immunology; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D007700:Kinetics; D018950:Lipopolysaccharide Receptors / Q000032:analysis; D008565:Membrane Proteins / Q000032:analysis / Q000235:genetics*; D009000:Monocytes / Q000737:chemistry / Q000166:cytology / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011917:Rats, Inbred Lew; D018121:Receptors, Cytokine / Q000032:analysis / Q000235:genetics*; D015728:Receptors, HIV / Q000032:analysis / Q000235:genetics*; D012995:Solubility; D013582:Synovial Fluid / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000737:chemistry / Q000276:immunology; D013643:Tarsus, Animal / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015854:Up-Regulation / Q000276:immunology
D017252:CD3 Complex; D000073883:CX3C Chemokine Receptor 1; C515538:CX3CL1 protein, human; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C; C515540:Cx3cl1 protein, rat; D007375:Interleukin-1; D018950:Lipopolysaccharide Receptors; D008565:Membrane Proteins; D012333:RNA, Messenger; D018121:Receptors, Cytokine; D015728:Receptors, HIV; D014409:Tumor Necrosis Factor-alpha