Antibodies bind and activate beta adrenergic and cholinergic lymphocyte receptors in Chagas' disease.
It is demonstrated that murine chagasic IgG and the corresponding F(ab')2 fragments interfere with beta adrenergic and muscarinic cholinergic specific ligand occupancy on T cell-enriched population. From the interaction between chagasic IgG or F(ab')2 with Lyt-1+ cells, an increase in cAMP levels occurs as a consequence of beta adrenergic receptor activation. On the contrary, chagasic IgG or F(ab')2 interactions with Lyt-2+ cells induce an activation of muscarinic cholinergic receptor, leading to an increment in cGMP. Muscarinic cholinergic and beta adrenergic stimulation trigger the release of PGE2 and TXB2, respectively. Lyt-2+ cells treated with chagasic IgG or F(ab')2 are able to decrease the contractility of mouse atria. The same negative inotropic effect is elicited with Lyt-2+ cells from Trypanosoma cruzi-infected mice susceptible to developed myocarditis. The implications of these results in the pathogenesis of Chagas' myocarditis are discussed.
Gorelik
G
G
Centro de Estudios Farmacológicos y de Principios Naturales, Facultad de Medicina, Universidad de Buenos Aires, Argentina.
Genaro
A M
AM
Sterin-Borda
L
L
Gonzalez Cappa
S
S
Borda
E S
ES
D000818:Animals; D016275:Atrial Function; D014355:Chagas Disease / Q000097:blood*; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D007140:Immunoglobulin Fab Fragments / Q000378:metabolism; D007074:Immunoglobulin G / Q000378:metabolism*; D008214:Lymphocytes / Q000648:ultrastructure*; D051379:Mice; D008807:Mice, Inbred BALB C; D009200:Myocardial Contraction / Q000187:drug effects; D011485:Protein Binding; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D011950:Receptors, Cholinergic; D013601:T-Lymphocytes / Q000378:metabolism; D013929:Thromboxane B2 / Q000378:metabolism
D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D011943:Receptors, Adrenergic, beta; D011950:Receptors, Cholinergic; D013929:Thromboxane B2; D000242:Cyclic AMP; D006152:Cyclic GMP; D015232:Dinoprostone