Endothelial injury in internal organs of University of California at Davisline 200 (UCD 200) chickens, an animal model for systemic sclerosis (scleroderma)

Systemic sclerosis (SSc) is a multisystem disorder characterized by mononuc lear cell infiltration and fibrosis. Using skin samples from human SSc and UCD 200 chickens, which spontaneously develop a hereditary disease closely resembling human SSc, we have shown previously that endothelial cell apopto sis is a primary event in the pathogenesis of SSc. The aim of the present s tudy was to investigate the initial disease stage in visceral organs of UCD 200 chickens with special emphasis on endothelial apoptosis, mononuclear c ell infiltration and collagen deposition using tissue samples from oesophag us, lung, heart, kidney and Liver. Apoptotic endothelial cells were detecte d by terminal deoxynucleotidyl transferase-mediated FITC-dUTP nick end labe ling (TUNEL), mononuclear cell infiltrates were stained with hematoxylin an d eosin, and increased collagen deposition was demonstrated by Goldner stai ning. Apoptotic endothelial cells were detected in oesophagus, lung and kid ney of UCD 200 chickens at the initial stage of the disease. No apoptotic e ndothelial cells were found in heart or liver of UCD 200 or in visceral org ans of healthy normal UCD 058 control chickens. Oesophagus of UCD 200 chick ens, which was the most affected internal organ, showed mononuclear cell in filtrations and increased deposition of collagen. Perivascular inflammatory infiltrates and collagen deposition appeared later than endothelial cell. apoptosis. These data support the hypothesis that endothelial cell apoptosi s initiates the disease process, followed by mononuclear cell infiltration and fibrosis. (C) 2000 Academic Press.