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Titolo:
Novel human alpha 9 acetylcholine receptor regulating keratinocyte adhesion is targeted by pemphigus vulgaris autoimmunity
Autore:
Nguyen, VT; Ndoye, A; Grando, SA;
Indirizzi:
Univ Calif Davis, Med Ctr, Dept Dermatol, Sacramento, CA 95817 USA Univ Calif Davis Sacramento CA USA 95817 rmatol, Sacramento, CA 95817 USA
Titolo Testata:
AMERICAN JOURNAL OF PATHOLOGY
fascicolo: 4, volume: 157, anno: 2000,
pagine: 1377 - 1391
SICI:
0002-9440(200010)157:4<1377:NHA9AR>2.0.ZU;2-S
Fonte:
ISI
Lingua:
ENG
Soggetto:
BLISTER-CAUSING ANTIBODIES; COCHLEAR HAIR-CELLS; INOSITOL 1,4,5-TRISPHOSPHATE; PHARMACOLOGICAL PROPERTIES; PARANEOPLASTIC PEMPHIGUS; INTRACELLULAR CALCIUM; ANTIGEN DESMOGLEIN-3; MUSCARINIC RECEPTOR; CARCINOMA LINE; NEONATAL MICE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
82
Recensione:
Indirizzi per estratti:
Indirizzo: Grando, SA Univ Calif Davis, Med Ctr, Dept Dermatol, 4860 Y St,3400, Sacramento, CA 95817 USA Univ Calif Davis 4860 Y St,3400 Sacramento CA USA 95817817 USA
Citazione:
V.T. Nguyen et al., "Novel human alpha 9 acetylcholine receptor regulating keratinocyte adhesion is targeted by pemphigus vulgaris autoimmunity", AM J PATH, 157(4), 2000, pp. 1377-1391

Abstract

Pemphigus vulgaris (PV) is a potentially fatal autoimmune mucocutaneous blistering disease. It was assumed that PV is caused by anti-desmoglein (Dsg)3 autoimmunity because absorption of PV sera with a chimeric baculoproteincontaining the Dsg 3 and IgG1 portions, rDsg3-Ig-His, eliminated disease-causing antibodies. In this study we demonstrate that rDsg3-Ig-His adsorbs out autoantibodies to different keratinocyte antigens, including a non-Dsg 3130-kd polypeptide, Because the pool of disease-causing PV IgGs contains antibodies against the keratinocyte acetylcholine receptor (AChR), me soughtto identify the targeted receptor(s). Preincubation of monkey esophagus with PV antibodies blocked specific staining of the keratinocyte cell membrane with rabbit monoepitopic antibody to alpha 9 AChR, indicating that this first of its kind AChR with dual, muscarinic and nicotinic pharmacology is targeted by PV autoimmunity. Anti-alpha 9 antibody stained keratinocytes in a fishnet-like intercellular pattern, and visualized a single band at similar to 50 kd in Western blots of keratinocyte membrane proteins. Using step-by-step reverse transcription polymerase chain reactions with primers basedon known alpha 9 sequence regions, we identified the complete reading frame of human alpha 9. Its amino acid sequence showed 85% similarity with rat alpha 9. Treatment of keratinocyte monolayers with anti-alpha 9 antibody induced pemphigus-like acantholysis, which could be reversed either spontaneously or by using the cholinergic agonist carbachol. We conclude that alpha 9 is coupled to physiological regulation of keratinocyte adhesion, and its interaction with PV IgG may lead to blister development.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 25/11/20 alle ore 06:45:44