T lymphocytes from T. cruzi-infected mice alter heart contractility: participation of arachidonic acid metabolites.
T lymphocytes from T. cruzi infected mice susceptible to the development of myocarditis altered the contractility of normal mouse atria in vitro. While lymphocytes obtained from normal mice had no effect, lymphocytes from T. cruzi-infected mice cultured with normal atria induced negative or positive inotropic effects depending upon the post-infection period; negative inotropism was induced by lymphocytes obtained from animals at 1 to 4 weeks post-infection, and positive inotropism was induced by lymphocytes taken at 7 to 14 weeks post-infection. These effects were mediated by soluble factors as evidenced by the ability of lymphocyte culture supernatants to alter contractility. Cell enrichment experiments indicated that T lymphocytes rather than B lymphocytes were responsible for these inotropic effects. Lyt(2+)-enriched T lymphocytes were found to be responsible for triggering the negative inotropic effect at 3 weeks post-infection when myocarditis was less intense, whereas Lyt1(+)-enriched T lymphocytes induced the positive inotropic effect at 8 weeks after T. cruzi infection when myocarditis was severe. Furthermore, inhibitors of the cyclooxygenase pathway of arachidonic acid metabolism blunted the negative inotropic effect while inhibitors of lipoxygenase pathway inhibited the positive inotropic effect. PGE2 was found to be spontaneously released by Lyt(2+)-enriched T cells obtained at 3 weeks post-infection while LTC4 was released by atria cultured in the presence of Lyt 1+ T cells obtained at 8 weeks post-infection. In conclusion, these findings suggest that infiltrating T lymphocytes may contribute to myocardial dysfunction during T. cruzi infection by releasing or inducing the release of harmful arachidonic acid metabolites such as PGE2 and LTC4 which alter normal cardiac function.
Gorelik
G
G
Centro de Estudios Farmacológicos y Botánicos (CEFYBO), CONICET, Buenos Aires, Argentina.
Borda
E
E
Postan
M
M
Gonzalez Cappa
S
S
Sterin-Borda
L
L
D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism*; D001402:B-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D014355:Chagas Disease / Q000276:immunology* / Q000378:metabolism; D008084:Lipoxygenase / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009200:Myocardial Contraction / Q000276:immunology; D009205:Myocarditis / Q000276:immunology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000502:physiology
D001095:Arachidonic Acids; D008084:Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases