Related Experiment Videos
Functionally active cardiac antibodies in chronic Chagas' disease are specifically blocked by Trypanosoma cruzi
M O Masuda1, M Levin, S F De Oliveira
1Instituto de Biofisica Carlos Chagas Filho, CCS, UFRJ, Brazil.
Abstract:
Antibodies of chronic chagasic patients have been shown to interfere with electric and mechanical activities of cardiac embryonic myocytes in culture and with whole mammalian hearts. A mechanism proposed for this effect involves interaction of the antibodies with G-protein-linked membrane receptors, thus leading to activation of beta adrenergic and muscarinic receptors; more specifically, IgG of chagasic patients would interact with the negatively charged regions of the second extracellular loop of these receptors. We performed competition experiments to test this hypothesis. We evaluated the effect of sera/IgG from patients previously known to depress electrogenesis and/or atrioventricular conduction in isolated rabbit hearts after incubation with live and lysed parasites, the peptide corresponding to the second extracellular loop (O2) of the M2 receptor, and different peptides derived from two ribosomal proteins of T. cruzi: P0 and P2beta. Our results indicate that 1) the antigenic factor inducing the functionally active IgGs in the chagasic patients is probably an intracellular T. cruzi antigen; 2) IgG/serum is interacting with the O2 region of the M2 receptor in the rabbit heart; and 3) the negative charges present in the ribosomal proteins of T. cruzi are important in mediating the interaction between the patients' serum/IgG and the receptor.
Insights
Chagas disease antibodies disrupt heart function by targeting specific receptor regions. This study identifies intracellular parasite antigens and ribosomal protein charges as key factors in this autoimmune cardiac response.
Area of Science:
- Immunology
- Cardiology
- Parasitology
Background:
- Antibodies from Chagas disease patients affect cardiac electrical and mechanical activity.
- A proposed mechanism involves antibody interaction with G-protein-linked membrane receptors, activating adrenergic and muscarinic receptors.
Purpose of the Study:
- To test the hypothesis that Chagasic IgG interacts with the second extracellular loop of M2 receptors.
- To identify the specific T. cruzi antigens responsible for inducing these cardiac-affecting antibodies.
Main Methods:
- Competition experiments using sera/IgG from Chagasic patients.
- Incubation with live/lysed T. cruzi, M2 receptor extracellular loop peptide (O2), and T. cruzi ribosomal protein peptides (P0, P2beta).
- Evaluation of effects on electrogenesis and atrioventricular conduction in isolated rabbit hearts.
Main Results:
- The antigenic factor is likely an intracellular T. cruzi antigen.
- Chagasic IgG/serum interacts with the O2 region of the M2 receptor in rabbit hearts.
- Negative charges on T. cruzi ribosomal proteins are crucial for the IgG-receptor interaction.
Conclusions:
- Intracellular T. cruzi antigens induce antibodies that target M2 receptors in the heart.
- The interaction involves specific negatively charged regions on T. cruzi ribosomal proteins and the M2 receptor's extracellular loop.
- This finding elucidates a mechanism for Chagasic cardiomyopathy and suggests potential therapeutic targets.