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Titolo:
Anti-SSA/Ro and anti-SSB/La autoantibodies bind the surface of apoptotic fetal cardiocytes and promote secretion of TNF-alpha by macrophages
Autore:
Miranda-Carus, ME; Askanase, AD; Clancy, RM; Di Donato, F; Chou, TM; Libera, MR; Chan, EKL; Buyon, JP;
Indirizzi:
NYU, Hosp Joint Dis, Sch Med, Dept Rheumatol, New York, NY 10003 USA NYU New York NY USA 10003 Sch Med, Dept Rheumatol, New York, NY 10003 USA Stevens Inst Technol, Dept Chem Biochem & Mat Engn, Hoboken, NJ 07030 USA Stevens Inst Technol Hoboken NJ USA 07030 Mat Engn, Hoboken, NJ 07030 USA Scripps Clin & Res Inst, La Jolla, CA 92037 USA Scripps Clin & Res Inst La Jolla CA USA 92037 nst, La Jolla, CA 92037 USA
Titolo Testata:
JOURNAL OF IMMUNOLOGY
fascicolo: 9, volume: 165, anno: 2000,
pagine: 5345 - 5351
SICI:
0022-1767(20001101)165:9<5345:AAAABT>2.0.ZU;2-4
Fonte:
ISI
Lingua:
ENG
Soggetto:
CONGENITAL HEART-BLOCK; SYSTEMIC LUPUS-ERYTHEMATOSUS; NEONATAL LUPUS; CARDIAC MYOCYTES; IMMUNE-RESPONSE; CELL-SURFACE; MOTHERS; ANTIBODIES; MECHANISMS; MOLECULES;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
30
Recensione:
Indirizzi per estratti:
Indirizzo: Buyon, JP NYU, Hosp Joint Dis, Sch Med, Dept Rheumatol, Room 1608,301 E 17th St, NewYork, NY 10003 USA NYU Room 1608,301 E 17th St New York NY USA 10003 , NY 10003 USA
Citazione:
M.E. Miranda-Carus et al., "Anti-SSA/Ro and anti-SSB/La autoantibodies bind the surface of apoptotic fetal cardiocytes and promote secretion of TNF-alpha by macrophages", J IMMUNOL, 165(9), 2000, pp. 5345-5351

Abstract

Despite the near universal association of congenital heart block and maternal Abs to SSA/Ro and SSB/La, the intracellular location of these Ags has made it difficult to substantiate their involvement in pathogenicity. To define whether components of the SSA/Ro-SSB/La complex, which translocate during apoptosis, are indeed accessible to extracellular Abs, two approaches were taken: immunoprecipitation of surface biotinylated proteins and scanningelectron microscopy. Human fetal cardiocytes from 16-24-wk abortuses were cultured and incubated with staurosporine to induce apoptosis, Surface biotinylated 48-kDa SSB/La was reproducibly immunoprecipitated from apoptotic, but not nonapoptotic cardiocytes, Surface expression of SSA/Ro and SSB/La was further substantiated by scanning electron microscopy, Gold particles (following incubation with gold-labeled sera containing various specificitiesof anti-SSA/Ro-SSB/La Abs and murine mAb to SSB/La and 60-kDa SSA/Ro) wereconsistently observed on early and late apoptotic cardiocytes. No particles were seen after incubation with control antisera. To evaluate whether opsonized apoptotic cardiocytes promote inflammation, cells were cocultured with macrophages. Compared with nonapoptotic cardiocytes or apoptotic cardiocytes incubated with normal sera, apoptotic cardiocytes preincubated with affinity-purified Abs to SSB/La, 52-kDa SSA/Ro, or 60-kDa SSA/Ro increased the secretion of TNF-alpha from cocultured macrophages. In summary, apoptosisresults in surface accessibility of all SSA/Ro-SSB/La Ags for recognition by circulating maternal Abs. It is speculated that in vivo such opsonized apoptotic cardiocytes promote an inflammatory response by resident macrophages with damage to surrounding conducting tissue.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 21/09/20 alle ore 06:29:11