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Impaired clearance of apoptotic cardiocytes is linked to anti-SSA/Ro and -SSB/La antibodies in the pathogenesis of
Robert M Clancy1, Petra J Neufing, Ping Zheng
1Department of Medicine, Division of Rheumatology, New York University School of Medicine, New York, New York 10016, USA. bodbclancy@aol.com
The Journal of Clinical Investigation
|August 15, 2006
Summary
Resident cardiocytes clear apoptotic cells via phosphatidylserine receptors. Maternal autoantibodies against SSA/Ro and SSB/La inhibit this clearance, potentially causing inflammation and scarring in congenital heart block.
Area of Science:
- Cardiology
- Immunology
- Cell Biology
Background:
- Apoptosis is a normal cellular process.
- Cardiocytes play a role in clearing apoptotic cells.
- Maternal autoantibodies are implicated in congenital heart block (CHB).
Purpose of the Study:
- To investigate the role of cardiocytes in clearing apoptotic cells.
- To determine the effect of anti-SSA/Ro and anti-SSB/La antibodies on this process.
- To explore the mechanism linking maternal autoantibodies to CHB.
Main Methods:
- Induction of apoptosis in fetal cardiocytes via extrinsic and intrinsic pathways.
- Coculturing healthy and apoptotic cardiocytes.
- Assessment of phagocytic uptake using microscopy and antibody blocking.
- In vivo studies using a murine model.
Main Results:
- Cardiocytes express phosphatidylserine receptors (PSRs) involved in apoptotic cell clearance.
- Anti-SSA/Ro and anti-SSB/La antibodies inhibited apoptotic cardiocyte uptake.
- IgG from mothers of CHB children blocked clearance.
- Anti-Ro60 binding inhibited uptake in wild-type but not knockout mice.
Conclusions:
- Resident cardiocytes contribute to the physiologic clearance of apoptotic cells.
- Opsonization by maternal autoantibodies inhibits this clearance mechanism.
- Inhibition of clearance may lead to apoptotic cell accumulation, inflammation, and scarring, potentially contributing to CHB.
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