Discrepant expression of neprilysin on fibroblasts in diffuse systemic sclerosis

Objective. Neprilysin (NEP; EC3.4.24.11) is an ectopeptidase mainly produce d by fibroblasts and cleaving a large number of neuropeptides. We previousl y found increased plasma circulating levels of NEP in patients with systemi c sclerosis (SSc), but in SSc fibroblasts derived from the diffuse subset N EP was present in lower concentration. We evaluate in vitro fibroblasts of both subsets of the disease, diffuse and limited, the intracellular levels of NEP, and its expression as CD10 on the cellular surface. Methods, Fibroblasts, derived from biopsies taken from affected skin of 8 p atients with the limited subset and 5 with the diffuse subset, were grown i n vitro and intracellular levels of NEP activity were measured with a fluor ometric method, while CD10 surface expression was evaluated by FAGS analysi s. Cell proliferation was assessed by (3H)Thymidine incorporation. Results. Intracellular NEP activity was significantly increased in diffuse (7.02 +/- 4.8 pg/ml/min 10(6) cells) compared to limited SSc (1.11 +/- 2.0) and control fibroblasts (1.41 +/- 0.9). CD10 expression was significantly impaired on diffuse SSc fibroblasts (47.3 +/- 15%) compared to controls (74 .6 +/- 11%) and the limited subset (82.7 +/- 11%). Cell proliferation of di ffuse SSc fibroblasts was strikingly higher than controls and limited SSc f ibroblasts. Conclusion. These results confirm that NEP is produced by fibroblasts and i ndicate that in diffuse SSc fibroblasts NEP is produced in higher quantitie s, while the expression of the enzyme on the cell surface is significantly reduced. This condition may affect the proliferation rate of fibroblasts as well as the metabolism of various peptides.