Expression of the C5a receptor (CD88) on synovial mast cells in patients with rheumatoid arthritis.
OBJECTIVE
To analyze the immunophenotype and functional properties of synovial mast cells (SyMC) in patients with rheumatoid arthritis (RA) and osteoarthritis (OA).


METHODS
Synovial tissue was obtained from 25 patients with RA and 17 patients with OA. Tissue was dispersed by enzymatic digestion using collagenase. Surface receptor expression on SyMC was analyzed by monoclonal antibodies (MAb) and indirect immunofluorescence staining. Histamine release experiments were performed using the MC agonist recombinant human (rHu) stem cell factor (SCF), the anaphylatoxin rHuC5a, and an anti-IgE antibody.


RESULTS
In both groups of patients (RA and OA), SyMC were found to react with MAb to IgE, SCF receptor (c-kit, CD117), as well as CD antigens likewise expressed in lung MC (CD9, CD29, CD33, CD43, CD44, CD45). However, a significantly increased proportion of SyMC from RA patients reacted with MAb against C5a receptor (C5aR; CD88), compared with SyMC from OA (mean +/- SD percentage of SyMC reacting with CD88 MAb S5/1 in RA 27.5 +/- 8.6% versus 0.0% in OA, and with CD88 MAb W17/1 in RA 58.3 +/- 15.2% versus 12.5 +/- 15.0% in OA; P < 0.05). Furthermore, in RA, significant histamine release from SyMC above control was induced by rHuC5a, anti-IgE, and rHuSCF, whereas SyMC in OA released histamine after stimulation with anti-IgE and rHuSCF, but not rHuC5a.


CONCLUSIONS
SyMC exhibit phenotypic and functional properties similar to MC in other tissues. In patients with RA, but not OA, SyMC express significant amounts of C5aR (CD88) and release histamine in response to rHuC5a. These results indicate a role for SyMC and C5a/C5aR in the pathogenesis of RA.
Kiener
H P
HP
University of Vienna, Austria.
Baghestanian
M
M
Dominkus
M
M
Walchshofer
S
S
Ghannadan
M
M
Willheim
M
M
Sillaber
C
C
Graninger
W B
WB
Smolen
J S
JS
Valent
P
P
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000954:Antigens, Surface / Q000032:analysis; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D015936:Complement C5a / Q000378:metabolism*; D005260:Female; D006632:Histamine / Q000378:metabolism; D006801:Humans; D016130:Immunophenotyping; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D008875:Middle Aged; D011951:Receptors, Complement / Q000378:metabolism*; D018121:Receptors, Cytokine / Q000378:metabolism; D019089:Stem Cell Factor / Q000494:pharmacology; D013583:Synovial Membrane / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
D000954:Antigens, Surface; D011951:Receptors, Complement; D018121:Receptors, Cytokine; D019089:Stem Cell Factor; D015936:Complement C5a; D006632:Histamine