LOCALIZATION OF ENDOTHELIN-1 AND ITS BINDING-SITES IN SCLERODERMA SKIN

Objective. Endothelin-1 (ET-1) has been implicated in the pathogenesis of systemic sclerosis (SSc) as it is both a potent vasoconstrictor an d fibroblast mitogen and is raised in the circulation of patients with SSc and primary Raynaud's phenomenon. Methods. We examined the locali zation and level of expression of ET-1 and its putative receptors in c linically ''uninvolved'' (i.e., prescleroderma skin) and involved skin from patients with diffuse cutaneous systemic sclerosis (dcSSc), usin g the alkaline phosphatase antialkaline phosphatase technique while ET -1 binding sites were examined using in vitro autoradiography. Results . There was an increase in dermal ET-1 staining in clinically uninvolv ed and involved skin from patients with early active dcSSc compared wi th late stage fibrotic SSc skin and normal skin from healthy volunteer s. Increased ET-1 staining was associated predominantly with the super ficial vessels in the SSc skin sections. In addition, there was a sign ificant increase in [I-125]ET-1 binding to superficial vessels and the dermal/epidermal junction in SSc skin compared with the binding to si milar structures in normal tissue. There was no change in [I-125]ET-1 binding to the deep dermal vessels in both SSc and normal skin. This i ncrease in [I-125]ET-1 binding in SSe skin was not maintained with inc reasing tissue fibrosis. Conclusion. The presence of increased ET-1 le vels as well as its binding sites in both the prescleroderma and invol ved skin of patients with dcSSc compared to controls suggests that ET- 1 may play a role in the pathology of dermal fibrosis and vasoconstric tion in SSc.