Internalization of non-clustered desmoglein 1 without depletion of desmoglein 1 from adhesion complexes in an experimental model of the autoimmune disease pemphigus foliaceus.
Serum antibodies against desmoglein 1 (Dsg1) are known to induce the clinical and histological manifestations of pemphigus foliaceus (PF), autoimmune bullous disease targeting skin. The basic pathophysiological phenomenon of PF blistering is the disruption of epithelial integrity in the granular layer of the epidermis due to separation of keratinocytes from one another, or acantholysis. In this report we investigate the changes in subcellular distribution of Dsg1 in response to serum of patients with PF by using an in vitro model of PF. Immunofluorescence analysis on HaCaT cells indicates that non-clustered Dsg1 is markedly internalized after exposure to serum. However, binding of PF IgG to Dsg1-rich adhesion complexes (desmosomes) does not cause disruption of such structures nor depletion of clustered Dsg1, as revealed by colocalization of PF IgG and Dsg1 in a punctate staining on cell membrane 24 hours after treatment. Furthermore, morphological studies demonstrate that the dramatic alterations induced by PF sera are not the result of apoptotic programs. Taken together, our data strongly suggest that anti-Dsg1 antibodies from PF serum could cause the internalization of non-clustered Dsg1 and perturb the formation of new desmosomes but not directly disrupt Dsg1-containing junctions when stable contacts are already formed.
Lanza
A
A
Center of Craniofacial Malformations-MRI, 1st School of Medicine and Surgery, II University of Naples, Italy.
De Rosa
A
A
Femiano
F
F
Annese
P
P
Ruocco
E
E
Gombos
F
F
Lanza
M
M
Cirillo
N
N
D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D002460:Cell Line; D051183:Desmoglein 1 / Q000276:immunology / Q000378:metabolism*; D003896:Desmosomes / Q000378:metabolism; D006801:Humans; D051379:Mice; D008954:Models, Biological; D010392:Pemphigus / Q000097:blood / Q000276:immunology / Q000378:metabolism*; D011817:Rabbits
D051183:Desmoglein 1