RESUMO
Chagas' disease is an important cause of heart disfunction in Latin America. Previous works from our laboratory reproducing experimental Chagas' disease in mice, demonstrated that the affinity and density of cardiac beta-adrenergic receptors were altered during the acute, indeterminate and chronic phase in Albino Swiss mice inoculated with Trypanosoma cruzi. Keeping in mind that Propranolol is a beta-blocking agent that binds in the same receptors' site, which we have described as altered along T. cruzi infection. The present study was performed to determine if a beta-blocker treatment could prevent cardiac beta-receptors' disorders provoked by T. cruzi infection. Two different doses of Propranolol (9 and 40 mg/kg/day) were injected in the mice during 3 days; then they were infected with 7 x 10(4) parasites/mouse and propranolol was continued daily for one week. The results showed that the concentrations of propranolol used did not protect the beta-receptors' sites by administration of each doses.
Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Doença de Chagas/tratamento farmacológico , Ventrículos do Coração/fisiopatologia , Propranolol/uso terapêutico , Receptores Adrenérgicos beta/efeitos dos fármacos , Doença Aguda , Animais , Doença de Chagas/fisiopatologia , Masculino , Camundongos , Parasitemia/tratamento farmacológico , Propranolol/farmacologiaRESUMO
We report herein on the specific and autoimmune humoral response generated by the immunization of mice with the R13 synthetic peptide coupled to a carrier protein, OVA. This peptide corresponds to the C-terminal region of Trypanosoma cruzi ribosomal P1 and P2 proteins (EEEDDDMGFGLFD), a sequence that differs from the other eukariotic P consensus sequence (EESDDDMGFGLFD) only in a nonconservative amino acid substitution. The antibody response studied by ELISA revealed that all R13-immunized mice had antibodies against R13, consisting mainly of IgG1 and IgG2 isotypes, even though IgG3 and IgE isotypes were also observed. The self-reactivity of anti-R13 sera assayed by immunoblot, revealed that all sera contained IgG antibodies binding to mouse and human 38-kDa heart antigen. This antigenic band binds several immunoglobulin isotypes (IgG2 > IgG3 > IgE > IgG1). The specificity of anti-R13 antibodies analyzed by competitive inhibition of R13 ELISA using R13 and R7 (MGFGLFD) peptides revealed that the reactivity of the induced anti-P antibodies was not absorbed by R7. Therefore, the main immunogenic region of R13 for mouse would be EEEDDD, which contains the amino acid substitution. In parallel with this humoral response, both partial protection and heart damage were observed in R13-immunized mice. In fact, the R13-immunized mice showed significantly lower parasitemia and longer survival than the control animals. In addition, all R13-immunized mice showed electrocardiographic changes (bradycardia, prolonged PQ segment, and intraventricular conduction disturbances), which are typical findings in Chagas disease patients. This study represents the first definitive report in which one defined B-cell epitope, the single peptide R13 from T. cruzi, coupled to a carrier protein was able to induce specific and autoreactive antibodies as well as to generate heart functional alterations.
Assuntos
Miocárdio/imunologia , Fosfoproteínas/imunologia , Proteínas de Protozoários/imunologia , Trypanosoma cruzi/imunologia , Animais , Anticorpos Antiprotozoários/biossíntese , Anticorpos Antiprotozoários/imunologia , Autoanticorpos/biossíntese , Autoanticorpos/imunologia , Autoantígenos/imunologia , Doença de Chagas/imunologia , Doença de Chagas/patologia , Doença de Chagas/fisiopatologia , Relação Dose-Resposta Imunológica , Eletrocardiografia , Ensaio de Imunoadsorção Enzimática , Epitopos/imunologia , Feminino , Coração/fisiopatologia , Humanos , Imunização , Immunoblotting , Imunoglobulinas/biossíntese , Imunoglobulinas/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Miocárdio/patologia , Parasitemia/imunologia , Parasitemia/patologia , Parasitemia/fisiopatologia , Proteínas RibossômicasRESUMO
Chagas' disease presents complex physiopathogenic mechanism, many of them poorly understood, that in our country generally produce cardiac lesions. The acute phase related with the presence of the parasite is usually asymptomatic. This report studies if the amount of T. cruzi that induced acute infection could modify the myocardiopathy evolution. Previous works have shown that Albino Swiss mice inoculated with 45 tripomastigotes (AcL) presented alterations in the cardiac pharmacological response to adrenergic agonist and antagonist studied at 30 days post-infection (p.i). Mice inoculated with 7 x 10(4) parasites/animal showed similar behaviour at 7 days p.i. We studied the involvement of the affinity and density of cardiac beta receptors in both acute groups by binding with 3H/DHA. The AcH group presented less cardiac beta receptors number (p < 0.001), but their affinity was conserved. The AcL model presented significantly less affinity (p < 0.01) but density was not different from non infected animals. beta receptors' affinity of both infected groups were similar, but AcH density was significantly diminished when compared with AcL. These studies demonstrates that the amount of T. cruzi received by the host determines and acelerates the evolution of the chagasic myocardiopathy.