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, prolife ration of MC precursors, mediates MC adhesion, and changes MC releasability ). We investigated expression of SCF and c-kit in synovial membrane with pa rticular reference to the mechanism of local MC hyperplasia and inflammatio n in arthritis. Methods. We conducted single and double labeling immunohistochemistry (ABC, APAAP, indirect immunofluorescence techniques) with antibodies to SCE c-ki t, MC tryptase, Ki-67 antigen (marker for proliferating cells), and CD68 (m onocyte/macrophage marker). Synovial specimens analyzed were from 31 patien ts: traumatic arthritis (TrA, n=9), osteoarthritis (OA, n=12), and rheumato id arthritis (RAI 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, wherea s SCF is detected in synovial lining cells, stromal fibroblasts, monocyte/m acrophages, endothelial cells, and in vascular basement membranes. SCF stai ning was localized to MC as well, but it was not possible to specify whethe r this represents SCF produced by or bound (via c-kit) to MC. Ln inflamed s ynovial membranes/areas, SCF was found to be redistributed into the extrace llular matrix. Redistribution of SCF was accompanied by degranulation and/o r accumulation of c-kit+ MC, the hyperplasia of which correlated positively with histologic inflammation/inflammatory cell densities, but did not :app ear to involve MC proliferation in situ. These findings appeared to be comm on for all the conditions (TrA, OA, RA) studied. Conclusion. 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 i n the development of synovial MC hyperplasia without inducing in situ proli feration of MC, and that the synovial SCF/MC c-kit system may contribute to the local nonspecific inflammatory response/arthritic flares in TrA, OA, a nd RA.