Functional expression of the chemokine receptor CCR7 on fibroblast-like synoviocytes.
OBJECTIVE
We have characterized the expression and the function of the chemokine receptor CCR7 on fibroblast-like synoviocytes (FLS) of patients with RA and OA and on dermal fibroblasts.


METHODS
FLS were obtained after enzymatic digestion of synovial tissue (ST) of patients with RA and OA undergoing knee replacement surgery and taken into culture for chemokine receptor analysis by RT-PCR, flow cytometry and functional tests. Immunofluorescence for CCR7, fibroblast and T-cell markers was performed on ST of RA and OA patients. To study the response of FLS to CCR7 ligands and other chemokines, migration assays were performed in modified Boyden chambers. After stimulation of FLS with CCR7 ligands, the secretion of VEGF was evaluated by ELISA and Luminex.


RESULTS
CCR7 is expressed on FLS of patients with RA and OA, but not on dermal fibroblasts. FLS migrated in response to the CCR7 ligands, CCL19 and CCL21. Stimulation of FLS with CCL19 resulted in a significantly increased secretion of VEGF of RA- and OA-FLS.


CONCLUSIONS
Apart from the migration of FLS in response to CCL19 and CCL21, it was shown that activation of the CCR7 receptor on FLS results in an enhanced VEGF secretion. A considerable expression of CCR7 ligands in proximity to perivascular infiltrates has previously been described in inflamed synovial tissue of RA patients. Stimulation of FLS via CCR7 could thereby contribute to angiogenesis in the synovial tissue.
Brühl
H
H
Department of Internal Medicine I, University Hospital, 93042 Regensburg, Germany. hilke.bruehl@klinik.uni-regensburg.de
Mack
M
M
Niedermeier
M
M
Lochbaum
D
D
Schölmerich
J
J
Straub
R H
RH
D001172:Arthritis, Rheumatoid / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D054415:Chemokine CCL19 / Q000494:pharmacology; D002633:Chemotaxis; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D015355:Glaucoma, Neovascular / Q000378:metabolism; D006801:Humans; D008024:Ligands; D010003:Osteoarthritis / Q000378:metabolism* / Q000473:pathology; D054400:Receptors, CCR7 / Q000378:metabolism*; D013583:Synovial Membrane / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
C515460:CCL19 protein, human; C515370:CCR7 protein, human; D054415:Chemokine CCL19; D008024:Ligands; D054400:Receptors, CCR7; D014409:Tumor Necrosis Factor-alpha; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A