Anti-cell surface pemphigus autoantibody stimulates plasminogen activator activity of human epidermal cells. A mechanism for the loss of epidermal cohesion and blister formation

K. Hashimoto, K. M. Shafran, P. S. Webber, Gerald Sylvan Lazarus, K. H. Singer

Research output: Contribution to journalArticle

Abstract

Binding of anti-cell surface pemphigus autoantibodies to cultured human epidermal cells stimulates synthesis and secretion of plasminogen activator (PA). Increases in PA activity were detected within 6 h of the addition of IgG and stimulation was dependent upon IgG concentration. Stimulation of PA activity was inhibited by cycloheximide, which indicates that synthesis of protein was necessary. Pharmacological doses of dexamethasone also prevented IgG-induced stimulation of PA. Electrophoretic profiles of PA secreted by cultured human epidermal cells in the presence or absence of pemphigus IgG were similar. The majority of the PA activity comigrated with the higher-molecular-weight species of human urokinase (~55,000). Explants of normal human skin incubated with pemphigus vulgaris IgG displayed the loss of epidermal cohesion similar to that observed in patient biopsies. The histologic changes were potentiated by the inclusion of human plasminogen. Loss of epidermal cohesion in normal skin explants incubated with pemphigus foliaceous IgG was dependent upon the addition of plasminogen and was inhibited by aprotinin or lima bean trypsin inhibitor, which indicated that plasmin is the active enzyme in producing acantholysis. These data support the hypothesis that stimulation of PA by the anti-cell surface autoantibodies of pemphigus results in a localized increase in plasmin, which through proteolysis produces the loss of epidermal cohesion characterisic of pemphigus.

Original languageEnglish (US)
Pages (from-to)259-272
Number of pages14
JournalJournal of Experimental Medicine
Volume157
Issue number1
DOIs
StatePublished - 1983
Externally publishedYes

Fingerprint

Pemphigus
Plasminogen Activators
Blister
Human Activities
Autoantibodies
Immunoglobulin G
Plasminogen
Fibrinolysin
Acantholysis
Skin
Aprotinin
Trypsin Inhibitors
Urokinase-Type Plasminogen Activator
Cycloheximide
Dexamethasone
Proteolysis
Molecular Weight
Pharmacology
Biopsy
Enzymes

ASJC Scopus subject areas

  • Immunology

Cite this

@article{425e408e7fb24dd1aa542e8c56baef53,
title = "Anti-cell surface pemphigus autoantibody stimulates plasminogen activator activity of human epidermal cells. A mechanism for the loss of epidermal cohesion and blister formation",
abstract = "Binding of anti-cell surface pemphigus autoantibodies to cultured human epidermal cells stimulates synthesis and secretion of plasminogen activator (PA). Increases in PA activity were detected within 6 h of the addition of IgG and stimulation was dependent upon IgG concentration. Stimulation of PA activity was inhibited by cycloheximide, which indicates that synthesis of protein was necessary. Pharmacological doses of dexamethasone also prevented IgG-induced stimulation of PA. Electrophoretic profiles of PA secreted by cultured human epidermal cells in the presence or absence of pemphigus IgG were similar. The majority of the PA activity comigrated with the higher-molecular-weight species of human urokinase (~55,000). Explants of normal human skin incubated with pemphigus vulgaris IgG displayed the loss of epidermal cohesion similar to that observed in patient biopsies. The histologic changes were potentiated by the inclusion of human plasminogen. Loss of epidermal cohesion in normal skin explants incubated with pemphigus foliaceous IgG was dependent upon the addition of plasminogen and was inhibited by aprotinin or lima bean trypsin inhibitor, which indicated that plasmin is the active enzyme in producing acantholysis. These data support the hypothesis that stimulation of PA by the anti-cell surface autoantibodies of pemphigus results in a localized increase in plasmin, which through proteolysis produces the loss of epidermal cohesion characterisic of pemphigus.",
author = "K. Hashimoto and Shafran, {K. M.} and Webber, {P. S.} and Lazarus, {Gerald Sylvan} and Singer, {K. H.}",
year = "1983",
doi = "10.1084/jem.157.1.259",
language = "English (US)",
volume = "157",
pages = "259--272",
journal = "Journal of Experimental Medicine",
issn = "0022-1007",
publisher = "Rockefeller University Press",
number = "1",

}

TY - JOUR

T1 - Anti-cell surface pemphigus autoantibody stimulates plasminogen activator activity of human epidermal cells. A mechanism for the loss of epidermal cohesion and blister formation

AU - Hashimoto, K.

AU - Shafran, K. M.

AU - Webber, P. S.

AU - Lazarus, Gerald Sylvan

AU - Singer, K. H.

PY - 1983

Y1 - 1983

N2 - Binding of anti-cell surface pemphigus autoantibodies to cultured human epidermal cells stimulates synthesis and secretion of plasminogen activator (PA). Increases in PA activity were detected within 6 h of the addition of IgG and stimulation was dependent upon IgG concentration. Stimulation of PA activity was inhibited by cycloheximide, which indicates that synthesis of protein was necessary. Pharmacological doses of dexamethasone also prevented IgG-induced stimulation of PA. Electrophoretic profiles of PA secreted by cultured human epidermal cells in the presence or absence of pemphigus IgG were similar. The majority of the PA activity comigrated with the higher-molecular-weight species of human urokinase (~55,000). Explants of normal human skin incubated with pemphigus vulgaris IgG displayed the loss of epidermal cohesion similar to that observed in patient biopsies. The histologic changes were potentiated by the inclusion of human plasminogen. Loss of epidermal cohesion in normal skin explants incubated with pemphigus foliaceous IgG was dependent upon the addition of plasminogen and was inhibited by aprotinin or lima bean trypsin inhibitor, which indicated that plasmin is the active enzyme in producing acantholysis. These data support the hypothesis that stimulation of PA by the anti-cell surface autoantibodies of pemphigus results in a localized increase in plasmin, which through proteolysis produces the loss of epidermal cohesion characterisic of pemphigus.

AB - Binding of anti-cell surface pemphigus autoantibodies to cultured human epidermal cells stimulates synthesis and secretion of plasminogen activator (PA). Increases in PA activity were detected within 6 h of the addition of IgG and stimulation was dependent upon IgG concentration. Stimulation of PA activity was inhibited by cycloheximide, which indicates that synthesis of protein was necessary. Pharmacological doses of dexamethasone also prevented IgG-induced stimulation of PA. Electrophoretic profiles of PA secreted by cultured human epidermal cells in the presence or absence of pemphigus IgG were similar. The majority of the PA activity comigrated with the higher-molecular-weight species of human urokinase (~55,000). Explants of normal human skin incubated with pemphigus vulgaris IgG displayed the loss of epidermal cohesion similar to that observed in patient biopsies. The histologic changes were potentiated by the inclusion of human plasminogen. Loss of epidermal cohesion in normal skin explants incubated with pemphigus foliaceous IgG was dependent upon the addition of plasminogen and was inhibited by aprotinin or lima bean trypsin inhibitor, which indicated that plasmin is the active enzyme in producing acantholysis. These data support the hypothesis that stimulation of PA by the anti-cell surface autoantibodies of pemphigus results in a localized increase in plasmin, which through proteolysis produces the loss of epidermal cohesion characterisic of pemphigus.

UR - http://www.scopus.com/inward/record.url?scp=0020675063&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0020675063&partnerID=8YFLogxK

U2 - 10.1084/jem.157.1.259

DO - 10.1084/jem.157.1.259

M3 - Article

C2 - 6681540

AN - SCOPUS:0020675063

VL - 157

SP - 259

EP - 272

JO - Journal of Experimental Medicine

JF - Journal of Experimental Medicine

SN - 0022-1007

IS - 1

ER -