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Relationship between keratinocyte adhesion and death: anoikis in acantholytic diseases
R Gniadecki1, G B Jemec, B M Thomsen
1Department of Dermatology, University of Copenhagen, Bispebjerg Hospital, Denmark.
Abstract:
Loss of attachment to the substratum may trigger apoptosis in epithelial cells (anoikis). It is less clear whether apoptosis may be triggered by disruption of cell-cell contacts, as happens in acantholytic diseases. Biopsy specimens were obtained from the border of skin lesions from four patients with pemphigus vulgaris (PV), four patients with pemphigus foliaceus (PF), three patients with Darier's disease (DD), two patients with Darier's-type Grover's disease (GD), and two patients with benign familial pemphigus Hailey-Hailey disease (HH). Control skin was obtained from five healthy volunteers. TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling) and confocal laser scanning microscopy was employed to detect the nuclei containing fragmented DNA in apoptotic cells. In PV and PF, TUNEL-stained apoptotic keratinocytes were abundantly present in the regions of acantholysis and in the cohesive epidermis below the blisters. Apoptotic keratinocytes had pyknotic, condensed nuclei. In DD, GD and HH, the number of TUNEL-stained keratinocytes was lower, apoptotic keratinocytes were confined to the regions of dyskeratosis and acantholysis, and pyknosis was absent. In conclusion, disruption of cell-cell contacts in acantholytic skin disorders may in some cases cause apoptosis of keratinocytes. Further studies are needed to determine whether the observed differences in the pattern of apoptosis are due to targeting of different junctional elements (adherens junctions in PV and PF versus desmosomes in DD, GD and HH).
Insights
Disruption of cell-cell contacts in skin diseases like pemphigus vulgaris can trigger keratinocyte apoptosis. Differences in apoptosis patterns suggest distinct cellular mechanisms in various acantholytic disorders.
Area of Science:
- Dermatology
- Cell Biology
- Pathology
Background:
- Anoikis, or apoptosis due to loss of substratum attachment, is well-understood.
- The role of disrupted cell-cell contacts in triggering apoptosis, as seen in acantholytic diseases, is less clear.
Purpose of the Study:
- To investigate apoptosis in keratinocytes resulting from disrupted cell-cell contacts in various acantholytic skin disorders.
- To compare the patterns of apoptosis in pemphigus vulgaris (PV), pemphigus foliaceus (PF), Darier's disease (DD), Darier's-type Grover's disease (GD), and Hailey-Hailey disease (HH).
Main Methods:
- Biopsy specimens were collected from the border of skin lesions of patients with PV, PF, DD, GD, HH, and healthy volunteers.
- TUNEL staining and confocal laser scanning microscopy were used to detect apoptotic keratinocytes with fragmented DNA.
Main Results:
- Abundant TUNEL-stained apoptotic keratinocytes with pyknotic nuclei were observed in PV and PF, particularly in areas of acantholysis and below blisters.
- Fewer TUNEL-stained keratinocytes were found in DD, GD, and HH, confined to dyskeratosis and acantholysis regions, without pyknosis.
Conclusions:
- Disruption of cell-cell contacts in acantholytic skin disorders can induce keratinocyte apoptosis.
- Observed differences in apoptosis patterns may relate to the specific junctional elements targeted (adherens junctions vs. desmosomes).