thromboxane-b2 and Chagas-Disease

Trypanosoma cruzi induces inflammatory reactions in several tissues. The production of prostaglandin F2alpha, 6-keto-prostaglandin F1alpha and thromboxane B2, known to regulate the immune response and to participate in inflammatory reactions, was studied in mice experimentally infected with T. cruzi. The generation of nitric oxide (NO), which could be regulated by cyclooxygenase metabolites, was also evaluated. In the acute infection the extension of inflammatory infiltrates in skeletal muscle as well as the circulating levels of cyclooxygenase metabolites and NO were higher in resistant C3H mice than in susceptible BALB/c mice. In addition, the spontaneous release of NO by spleen cells increased earlier in the C3H mouse strain. In the chronic infections, the tissue inflammatory reaction was still prominent in both groups of mice, but a moderate increase of thromboxane B2 concentration and in NO released by spleen cells was observed only in C3H mice. This comparative study shows that these mediators could be mainly related to protective mechanisms in the acute phase, but seem not to be involved in its maintenance in the chronic T. cruzi infections.

Topics: Acute Disease; Animals; Chagas Disease; Chronic Disease; Dinoprostone; Disease Susceptibility; Epoprostenol; Inflammation; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C3H; Muscle, Skeletal; Nitric Oxide; Prostaglandin-Endoperoxide Synthases; Species Specificity; Spleen; Thromboxane A2; Thromboxane B2

Spasm and thrombosis of the coronary microcirculation has been implicated in the pathogenesis of the cardiomyopathy of Chagas' disease. We demonstrate that increases in platelet adherence and aggregation accompany Trypanosoma cruzi infection and may contribute to the observed microvascular pathology. Scanning electron microscopy and radiolabeled platelets studies revealed that platelet adherence to T. cruzi-infected human endothelial cells was significantly increased when compared to controls (P = 0.024). In in vitro experiments, we determined the influence of infection on prostacyclin production, a marker of endothelial cell perturbation. The basal levels of 6-keto-prostaglandin F1 alpha was significantly greater in the supernatant of infected endothelial cells than in those of uninfected endothelial cells (P less than 0.05). The influence of infection was assessed on platelet aggregation at days 5 and 12 post-infection in A/J mice. Platelets from T. cruzi-infected mice were 2-6-fold more sensitive to aggregation induced by adenosine diphosphate and sodium arachidonate than controls. Thromboxane B2 levels in the plasma of infected mice were greater than controls. These data support the hypothesis that heightened platelet reactivity and endothelial cell dysfunction are associated with acute Chagas' disease and may cause coronary microvascular spasm and/or occlusion.

Topics: Animals; Blood Platelets; Cells, Cultured; Chagas Cardiomyopathy; Chagas Disease; Coronary Vessels; Endothelium, Vascular; Epoprostenol; Female; Humans; Mice; Microcirculation; Microscopy, Electron, Scanning; Platelet Adhesiveness; Platelet Aggregation; Thromboxane B2

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.

Topics: Animals; Atrial Function; Chagas Disease; Cyclic AMP; Cyclic GMP; Dinoprostone; Immunoglobulin Fab Fragments; Immunoglobulin G; Lymphocytes; Mice; Mice, Inbred BALB C; Myocardial Contraction; Protein Binding; Receptors, Adrenergic, beta; Receptors, Cholinergic; T-Lymphocytes; Thromboxane B2