In vivo blockade of pemphigus vulgaris acantholysis by inhibition of intracellular signal transduction cascades.
BACKGROUND
Pemphigus vulgaris (PV) is an autoimmune disease characterized by mucocutaneous intraepithelial blisters and pathogenic autoantibodies against desmoglein 3. The mechanism of blister formation in pemphigus has not been defined; however, in vitro data suggest a role for activation of intracellular signalling cascades.


OBJECTIVE
To investigate the contribution of these signalling pathways to the mechanism of PV IgG-induced acantholysis in vivo.


METHODS
We used the passive transfer mouse model. Mice were injected with IgG fractions of sera from a patient with PV, with or without pretreatment with inhibitors of proteins that mediate intracellular signalling cascades.


RESULTS
Inhibitors of tyrosine kinases, phospholipase C, calmodulin and the serine/threonine kinase protein kinase C prevented PV IgG-induced acantholysis in vivo.


CONCLUSIONS
These observations strongly support the role of intracellular signalling cascades in the molecular mechanism of PV IgG-induced acantholysis.
Sánchez-Carpintero
I
I
Department of Dermatology, University Clinic of Navarra, School of Medicine, University of Navarra, PO Box 4209, Pamplona, Navarra, Spain.
España
A
A
Pelacho
B
B
López Moratalla
N
N
Rubenstein
D S
DS
Diaz
L A
LA
López-Zabalza
M J
MJ
D000051:Acantholysis / Q000209:etiology / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D000818:Animals; D015820:Cadherins / Q000276:immunology; D002147:Calmodulin / Q000037:antagonists & inhibitors / Q000502:physiology; D051184:Desmoglein 3; D004195:Disease Models, Animal; D006801:Humans; D007116:Immunization, Passive; D007074:Immunoglobulin G / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010392:Pemphigus / Q000150:complications*; D011494:Protein Kinases / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects*; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000502:physiology
D015820:Cadherins; D002147:Calmodulin; C071894:DSG3 protein, human; D051184:Desmoglein 3; D007074:Immunoglobulin G; D011494:Protein Kinases; D010738:Type C Phospholipases