Related Experiment Videos
Curvicircular intracytoplasmic membranous structures in keratinocytes of pemphigus foliaceus
1Department of Dermatology, Wayne State University School of Medicine, Detroit, Michigan 48201, USA.
Abstract:
We noticed intracytoplasmic membranous, annular, or circular structures in the lesion of pemphigus foliaceus and studied these by regular transmission electron microscopy and immunoelectron microscopy. These curvicircular bodies were observed in the preacantholytic keratinocytes of the blister wall as well as in acantholytic cells in 6 out of 6 patients with pemphigus foliaceus. They were absent in samples from 3 patients with pemphigus vulgaris. These structures were about 60-70 nm wide and consisted of 4 electron-dense layers. They were continuous with intact desmosomal structures and gap junctions in the periphery of the keratinocytes. These curvicircular membranous bodies were well labeled with immunogold particles for desmoglein, plakoglobin, connexin 43, and IgG. In contrast to pemphigus vulgaris, splitting of desmosomes through dissolution of intercellular desmoglea was seldom observed in all 6 specimens of pemphigus foliaceus. These findings suggest that in pemphigus foliaceus 1) curvicircular bodies are derived from internalized desmosomes and gap junctions, and 2) cell-to-cell adhesions are weakened by this internalization and acantholysis is initiated, while in pemphigus vulgaris the dissolution of desmoglea is the initial event. It is suggested that in pemphigus foliaceus the binding of autoantibody induces internalization of many intact desmosomes and gap junctions rather than splitting them.
Insights
In pemphigus foliaceus, unique circular structures derived from desmosomes and gap junctions are internalized, weakening cell adhesion. This contrasts with pemphigus vulgaris, where desmosome dissolution initiates blistering.
Area of Science:
- Dermatology
- Cell Biology
- Immunology
Background:
- Pemphigus foliaceus (PF) is an autoimmune blistering disease affecting keratinocyte adhesion.
- The precise mechanism of acantholysis in PF remains debated, particularly its initiation.
- Distinguishing PF from pemphigus vulgaris (PV) at the ultrastructural level is crucial.
Purpose of the Study:
- To investigate the ultrastructural basis of acantholysis in pemphigus foliaceus.
- To compare the cellular changes in PF with those observed in pemphigus vulgaris.
- To elucidate the role of specific cellular structures in the pathogenesis of PF.
Main Methods:
- Transmission electron microscopy (TEM) of skin lesions from PF and PV patients.
- Immunoelectron microscopy (IEM) using antibodies against desmoglein, plakoglobin, connexin 43, and IgG.
- Analysis of keratinocyte ultrastructure, including desmosomes and gap junctions.
Main Results:
- Intracytoplasmic curvicircular membranous bodies (60-70 nm wide, 4 electron-dense layers) were found in PF keratinocytes but not in PV.
- These bodies were continuous with intact desmosomes and gap junctions and labeled for desmoglein, plakoglobin, connexin 43, and IgG.
- Desmosome splitting was seldom observed in PF, unlike the dissolution of intercellular desmoglea seen in PV.
Conclusions:
- Curvicircular bodies in PF are likely internalized desmosomes and gap junctions.
- Internalization of these structures weakens cell-to-cell adhesion, initiating acantholysis in PF.
- This mechanism differs from PV, where desmoglea dissolution is the primary event.