OBJECTIVES: To examine the expression and concentrations of three ectopeptidases likely to be involved in regulating the functional levels of adhesion molecules and the turnover of connective tissue components, in patients with scleroderma (systemic sclerosis) (SSc) and in normal individuals. METHODS: Monoclonal antibodies against these antigens were used for immunoperoxidase staining of cryostat skin sections and for flow cytometric (fluorescence activated cell sorter) analysis of cultured dermal fibroblasts grown from SSc patients and normal controls. RESULTS: Although neutral endopeptidase-24.11 (NEP) (CD10) was not detected in either SSc or normal skin, aminopeptidase N (APN) (CD13) and dipeptidyl peptidase IV (DPPIV) (CD26) were both readily visualised. However, DPPIV appeared to be present in smaller concentrations in the SSc biopsy specimens. Moreover, while fibroblasts grown in vitro from both SSc and normal skin also had similar concentrations of APN, the expression of DPPIV in the cultured SSc cells was found to be very much less than that present in the normal fibroblasts. It is noteworthy that NEP, which was not detected in the tissue sections, was nevertheless readily detected in fibroblasts in culture. CONCLUSIONS: These results show that a number of cell surface proteases are expressed by dermal fibroblasts both in vivo and in vitro, and it is suggested that the marked downregulation of DPPIV in SSc could be at least partly responsible for the increased concentrations of adhesion molecules and matrix proteins associated with the molecular pathology of this disease.
OBJECTIVES: To examine the expression and concentrations of three ectopeptidases likely to be involved in regulating the functional levels of adhesion molecules and the turnover of connective tissue components, in patients with scleroderma (systemic sclerosis) (SSc) and in normal individuals. METHODS: Monoclonal antibodies against these antigens were used for immunoperoxidase staining of cryostat skin sections and for flow cytometric (fluorescence activated cell sorter) analysis of cultured dermal fibroblasts grown from SSc patients and normal controls. RESULTS: Although neutral endopeptidase-24.11 (NEP) (CD10) was not detected in either SSc or normal skin, aminopeptidase N (APN) (CD13) and dipeptidyl peptidase IV (DPPIV) (CD26) were both readily visualised. However, DPPIV appeared to be present in smaller concentrations in the SSc biopsy specimens. Moreover, while fibroblasts grown in vitro from both SSc and normal skin also had similar concentrations of APN, the expression of DPPIV in the cultured SSc cells was found to be very much less than that present in the normal fibroblasts. It is noteworthy that NEP, which was not detected in the tissue sections, was nevertheless readily detected in fibroblasts in culture. CONCLUSIONS: These results show that a number of cell surface proteases are expressed by dermal fibroblasts both in vivo and in vitro, and it is suggested that the marked downregulation of DPPIV in SSc could be at least partly responsible for the increased concentrations of adhesion molecules and matrix proteins associated with the molecular pathology of this disease.
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