RELATIONSHIP BETWEEN KERATINOCYTE ADHESION AND DEATH - ANOIKIS IN ACANTHOLYTIC DISEASES

Loss of attachment to the substratum may trigger apoptosis in epitheli al cells (anoikis), It is less clear whether apoptosis may be triggere d by disruption of cell-cell contacts, as happens in acantholytic dise ases, Biopsy specimens were obtained from the border of skill lesions from four patients with pemphigus vulgaris (PV), four patients with pe mphigus foliaceus (PF),three patients with Darier's disease (DD), two patients with Darier's-type Grover's disease (GD), and two patients wi th benign familial pemphigus Hailey-Hailey disease (HH), Control skin was obtained from five healthy volunteers, TUNEL (terminal deoxynucleo tidyl transferase-mediated dUTP nick end labelling) and confocal laser scanning microscopy was employed to detect the nuclei containing frag mented DNA in apoptotic cells, In PV and PF, TUNEL-stained apoptotic k eratinocytes were abundantly present in the regions of acantholysis an d in the cohesive epidermis below the blisters, Apoptotic keratinocyte s had pyknotic, condensed nuclei, In DD, GD and HH, the number of TUNE L-stained keratinocytes was lower, apoptotic keratinocytes were confin ed to the regions of dyskeratosis and acantholysis, and pyknosis was a bsent, In conclusion, disruption of cell-cell contacts in acantholytic skin disorders may in some cases cause apoptosis of keratinocytes. Fu rther studies are needed to determine whether the observed differences in the pattern of apoptosis are due to targeting of different junctio nal elements (adherens junctions in PV and PF versus desmosomes in DD, GD and HH).