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*
Hospital for Joint Diseases, New York University School of Medicine, New York, NY 10003;
Department of Obstetrics and Gynecology, Beth Israel Medical Center, New York, NY 10003; and
The Scripps Research Institute, La Jolla, CA 92037
Access of intracellular Ags SSA/Ro and SSB/La to cognate maternal
autoantibodies is unexplained despite their strong association with
congenital heart block. To investigate the hypothesis that apoptosis
facilitates surface accessibility of these Ags, human fetal cardiac
myocytes from 16- to 22-wk abortuses were established in culture using
a novel technique in which cells were isolated after perfusing the
aorta with collagenase. Confirmation of cardiac myocytes included
positive staining with antisarcomeric 
-actinin and contractility
induced by 1.8 mM calcium. Incubation with 0.5 µM staurosporine or
0.3 mM 2,3-dimethoxy-1,4-naphthoquinone induced the characteristic
morphologic and biochemical changes of apoptosis. The cellular topology
of Ro and La was evaluated with confocal microscopy and determined in
nonapoptotic and apoptotic cardiocytes by indirect immunofluorescence.
In permeabilized nonapoptotic cardiocytes, Ro and La were predominantly
nuclear, and propidium iodide (PI) stained the nucleus. In early
apoptotic cardiocytes, condensation of the PI- and Ro- or La-stained
nucleus was observed, accompanied by Ro/La fluorescence around the cell
periphery. In later stages of apoptosis, nuclear Ro and La staining
became weaker, and PI demonstrated nuclear fragmentation. Ro/La-stained
blebs emerged from the cell membrane, a finding observed in
nonpermeabilized cells, supporting an Ab-Ag interaction at the cell
surface. In summary, induction of apoptosis in cultured cardiocytes
results in surface translocation of Ro/La and recognition by Abs.
Although apoptotic cells are programmed to die and do not
characteristically evoke inflammation, binding of maternal Abs and
subsequent influx of leukocytes could damage surrounding healthy fetal
cardiocytes.
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