Soluble Fas ligand in the joints of patients with rheumatoid arthritis and osteoarthritis.
OBJECTIVE
To investigate the expression and function of Fas ligand (FasL),which can be in a membrane-bound or soluble form, in the joints of patients with rheumatoid arthritis (RA) and osteoarthritis (OA).


METHODS
The concentration of soluble FasL (sFasL) in serum and synovial fluid (SF) from 24 OA and 38 RA patients was measured using an enzyme-linked immunosorbent assay. The expression of FasL on SF lymphocytes (SFL) and peripheral blood lymphocytes (PBL) was assessed by reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. A cytotoxic killing assay of membrane-bound FasL and purified sFasL against cultured synovial cells was also performed.


RESULTS
Soluble FasL was detected in the SF of patients with RA and OA, but not in their serum. The concentration of SF sFasL was remarkably higher in patients with severe RA than in patients with mild RA or with OA. RT-PCR showed that SFL, but not PBL, from RA patients expressed messenger RNA for FasL. Membrane-bound FasL induced apoptosis in cultured synovial cells from the RA and OA patients, but naturally processed human sFasL did not.


CONCLUSIONS
SFL from RA patients expressed FasL, and cleaved sFasL accumulated in the SF of inflamed joints. The different killing activity of membrane-bound FasL and sFasL against synovial cells may regulate Fas-mediated apoptosis in synovial cells.
Hashimoto
H
H
Osaka University Medical School, and Osaka Bioscience Institute, Suita, Japan.
Tanaka
M
M
Suda
T
T
Tomita
T
T
Hayashida
K
K
Takeuchi
E
E
Kaneko
M
M
Takano
H
H
Nagata
S
S
Ochi
T
T
D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000494:pharmacology; D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D004305:Dose-Response Relationship, Drug; D053222:Fas Ligand Protein; D005260:Female; D015870:Gene Expression / Q000235:genetics; D006801:Humans; D007719:Knee Joint / Q000737:chemistry* / Q000473:pathology; D008214:Lymphocytes / Q000737:chemistry / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis* / Q000235:genetics / Q000276:immunology; D008565:Membrane Proteins / Q000494:pharmacology; D008875:Middle Aged; D010003:Osteoarthritis / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D012995:Solubility; D013582:Synovial Fluid / Q000737:chemistry / Q000378:metabolism; D013583:Synovial Membrane / Q000166:cytology / Q000187:drug effects
D000911:Antibodies, Monoclonal; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D012333:RNA, Messenger