Anti-SSA/Ro and anti-SSB/La autoantibodies bind the surface of apoptotic fetal cardiocytes and promote secretion of TNF-alpha by macrophages

Citation
Me. 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
Citations number
30
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Immunology
Journal title
JOURNAL OF IMMUNOLOGY
ISSN journal
0022-1767 → ACNP
Volume
165
Issue
9
Year of publication
2000
Pages
5345 - 5351
Database
ISI
SICI code
0022-1767(20001101)165:9<5345:AAAABT>2.0.ZU;2-4
Abstract
Despite the near universal association of congenital heart block and matern al Abs to SSA/Ro and SSB/La, the intracellular location of these Ags has ma de it difficult to substantiate their involvement in pathogenicity. To defi ne whether components of the SSA/Ro-SSB/La complex, which translocate durin g apoptosis, are indeed accessible to extracellular Abs, two approaches wer e taken: immunoprecipitation of surface biotinylated proteins and scanning electron microscopy. Human fetal cardiocytes from 16-24-wk abortuses were c ultured and incubated with staurosporine to induce apoptosis, Surface bioti nylated 48-kDa SSB/La was reproducibly immunoprecipitated from apoptotic, b ut not nonapoptotic cardiocytes, Surface expression of SSA/Ro and SSB/La wa s further substantiated by scanning electron microscopy, Gold particles (fo llowing incubation with gold-labeled sera containing various specificities of anti-SSA/Ro-SSB/La Abs and murine mAb to SSB/La and 60-kDa SSA/Ro) were consistently observed on early and late apoptotic cardiocytes. No particles were seen after incubation with control antisera. To evaluate whether opso nized apoptotic cardiocytes promote inflammation, cells were cocultured wit h macrophages. Compared with nonapoptotic cardiocytes or apoptotic cardiocy tes incubated with normal sera, apoptotic cardiocytes preincubated with aff inity-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, apoptosis results in surface accessibility of all SSA/Ro-SSB/La Ags for recognition b y circulating maternal Abs. It is speculated that in vivo such opsonized ap optotic cardiocytes promote an inflammatory response by resident macrophage s with damage to surrounding conducting tissue.