Expression of stem cell factor (SCF) and SCF receptor (c-kit) in synovial membrane in arthritis: correlation with synovial mast cell hyperplasia and inflammation.
OBJECTIVE
Stem cell factor (SCF), the ligand for the SCF receptor (c-kit) expressed on precursors and mature mast cells (MC), is a major agonist for human MC (e.g., SCF induces MC development, chemotaxis, activation, proliferation of MC precursors, mediates MC adhesion, and changes MC releasability). We investigated expression of SCF and c-kit in synovial membrane with particular reference to the mechanism of local MC hyperplasia and inflammation in arthritis.


METHODS
We conducted single and double labeling immunohistochemistry (ABC, APAAP, indirect immunofluorescence techniques) with antibodies to SCF, c-kit, MC tryptase, Ki-67 antigen (marker for proliferating cells), and CD68 (monocyte/macrophage marker). Synovial specimens analyzed were from 31 patients: traumatic arthritis (TrA, n=9), osteoarthritis (OA, n=12), and rheumatoid arthritis (RA, n=10). Control experiments were performed on human lung, skin, and buccal mucosa tissues, on the HMC-1 mast cell line, and isolated lung MC. Morphometry was performed by computerized image analysis.


RESULTS
Synovial c-kit expression was found to be restricted to MC, whereas SCF is detected in synovial lining cells, stromal fibroblasts, monocyte/macrophages, endothelial cells, and in vascular basement membranes. SCF staining was localized to MC as well, but it was not possible to specify whether this represents SCF produced by or bound (via c-kit) to MC. In inflamed synovial membranes/areas, SCF was found to be redistributed into the extracellular matrix. Redistribution of SCF was accompanied by degranulation and/or accumulation of c-kit+ MC, the hyperplasia of which correlated positively with histologic inflammation/inflammatory cell densities, but did not appear to involve MC proliferation in situ. These findings appeared to be common for all the conditions (TrA, OA, RA) studied.


CONCLUSIONS
In addition to the demonstration/characterization of SCF and c-kit protein expression in human synovium, results of this study suggest the hypothesis that, in arthritis, local mobilization of SCF may play a role in the development of synovial MC hyperplasia without inducing in situ proliferation of MC, and that the synovial SCF/MC c-kit system may contribute to the local nonspecific inflammatory response/arthritic flares in TrA, OA, and RA.
Ceponis
A
A
ORTON Research Institute, Orthopaedic Hospital of the Invalid Foundation, Helsinki, Finland. Arnoldas.Ceponis@kruuna.Helsinki.Fi
Konttinen
Y T
YT
Takagi
M
M
Xu
J W
JW
Sorsa
T
T
Matucci-Cerinic
M
M
Santavirta
S
S
Bankl
H C
HC
Valent
P
P
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001168:Arthritis / Q000378:metabolism*; D002460:Cell Line; D005260:Female; D006801:Humans; D006965:Hyperplasia; D007150:Immunohistochemistry; D007249:Inflammation; D019394:Ki-67 Antigen / Q000032:analysis; D008168:Lung / Q000166:cytology / Q000378:metabolism; D008297:Male; D008407:Mast Cells / Q000473:pathology; D008875:Middle Aged; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis / Q000096:biosynthesis*; D019089:Stem Cell Factor / Q000032:analysis / Q000096:biosynthesis*; D013583:Synovial Membrane / Q000166:cytology / Q000378:metabolism* / Q000473:pathology
D019394:Ki-67 Antigen; D019089:Stem Cell Factor; D019009:Proto-Oncogene Proteins c-kit