ENDOTHELIAL-CELL APOPTOSIS IS A PRIMARY PATHOGENETIC EVENT UNDERLYINGSKIN-LESIONS IN AVIAN AND HUMAN SCLERODERMA

The mechanism that may cause degenerative fibrotic skin lesions was st udied in situ using skin biopsies from patients with systemic sclerosi s (SSc), localized scleroderma, or keloids, and at the initial disease stage in the University of California at Davis (UCD) lines 200/206 ch ickens, which develop a hereditary systemic connective tissue disease resembling human SSc and permit study of disease stages not accessible in humans. Frozen skin sections were analyzed simultaneously for apop tosis by terminal deoxynucleotidyl transferase-mediated FITC-dUTP nick end labeling and indirect immunofluorescence staining of cell markers with tetramethylrhodamine isothiocyanate conjugates. The results show ed that endothelial cells are clearly the first cells to undergo apopt osis in the skin of UCD-200/206 chickens, a process that seems to be i nduced by anti-endothelial cell antibodies. In human fibrotic skin dis eases, apoptotic endothelial cells could only be detected in early inf lammatory disease stages of SSc and localized scleroderma.