A possible cell-biologic mechanism involved in blister formation of bullous pemphigoid: anti-180-kD BPA antibody is an initiator.
In this short review, we summarize the results of our recent studies on the effects of anti-bullous-pemphigoid antigen (BPA) antibodies and BP sera on the hemidesmosome in cultured keratinocytes (DJM-1 cells) as examined by immunofluorescence microscopy. The 180-kD and the 230-kD BPAs localized on the basal plasma membrane showed a homogeneously dotted pattern in cells grown with low Ca2+ (0.07 mM), while they formed a peculiar concentric ring or arch (ring/arch) pattern in cells grown with high Ca2+ (1.87 mM). In addition, the 180-kD BPA was distributed also on the lateral/apical cell membrane, and the 230-kD BPA was found in the cytoplasm. The high Ca2+ ring/arch arrangement of BPAs was formed within 3 h after the low-high Ca2+ switch. Anti-180-kD BPA monoclonal antibodies (MAbs) and BP sera, but not anti-230-kD BPA MAbs, which were added into this system, caused the internalization of the 180-kD BPA from the lateral/apical cell membrane and inhibited the formation of the ring/arch pattern. These results suggest that autoantibodies to the 180-kD, but not to the 230-kD, BPAs may directly bind to the antigen on the cell surface of the basal cells and disturb the formation of hemidesmosomes. The 180-kD BPA appears to be an initiator of blister formation.
Kitajima
Y
Y
Department of Dermatology, Gifu University School of Medicine, Japan.
Hirako
Y
Y
Owaribe
K
K
Yaoita
H
H
D001323:Autoantibodies / Q000502:physiology*; D001324:Autoantigens / Q000097:blood / Q000276:immunology / Q000502:physiology; D001768:Blister / Q000150:complications / Q000503:physiopathology*; D002352:Carrier Proteins; D002462:Cell Membrane / Q000276:immunology; D002478:Cells, Cultured; D003094:Collagen; D003598:Cytoskeletal Proteins; D003896:Desmosomes / Q000276:immunology / Q000502:physiology; D000071821:Dystonin; D005455:Fluorescent Antibody Technique; D006801:Humans; D015603:Keratinocytes / Q000276:immunology / Q000648:ultrastructure; D008970:Molecular Weight; D009419:Nerve Tissue Proteins; D024041:Non-Fibrillar Collagens; D010391:Pemphigoid, Bullous / Q000150:complications / Q000276:immunology / Q000503:physiopathology*; D000097805:Collagen Type XVII
D001323:Autoantibodies; D001324:Autoantigens; D002352:Carrier Proteins; D003094:Collagen; D003598:Cytoskeletal Proteins; D000071821:Dystonin; D009419:Nerve Tissue Proteins; D024041:Non-Fibrillar Collagens; D000097805:Collagen Type XVII; C486268:DST protein, human