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by Macrophages1
*
Department of Rheumatology, Hospital for Joint Diseases, New York University School of Medicine, New York, NY 10003;
Department of Chemical, Biochemical and Materials Engineering, Stevens Institute of Technology, Hoboken, NJ 07030; and
The Scripps Research Institute, La Jolla, CA 92037
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 scanning electron 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
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 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-
from cocultured macrophages. In summary, apoptosis results
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.
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