Increased production of reactive oxygen species by cells from mice acutely infected with Trypanosoma cruzi

Abstract

Release of reactive oxygen species (ROS) by cells from BALB/c mice was studied during the acute stage of the infection with 50 bloodstream forms of Trypanosoma cruzi, Tulahuén strain. Production of ROS by spleen and peritoneal cells was evaluated by chemiluminescence using luminol as enhancer (CL-Lum). Three to four weeks after infection, CL-Lum response after the addition of opsonized zymosan to spleen and peritoneal cells from infected mice was 13 and 98 times, respectively, above the levels obtained with cells from noninfected mice. The kinetics of this hyperactivity was similar to that of the parasitemia. Both reached maximal values on the third to fourth weeks and decreased at 7 weeks postinfection. During this hyperactivation stage, spleen and peritoneal cells from infected mice showed a "spontaneous" CL-Lum response (without any stimulus added in vitro) absent in noninfected mice. Both, "spontaneous" and zymosan stimulated CL-Lum responses were inhibited by 100 microM azide and by 0.8 microM superoxide dismutase, suggesting the involvement of hemoproteins and superoxide anion in the measured responses. Moreover, spleen cells from acutely infected mice displayed a hyperactivity in the CL-Lum response when recombinant interferon-gamma was added in vitro. Supernatants of spleen cells from both normal or infected mice, stimulated in vitro with concanavalin A, contained similar levels of interferon and were equally able to stimulate the trypanocidal activity of normal macrophages. These results suggest that mediators of activation of phagocytic cells can be produced during acute T. cruzi infection. In addition, phagocytic cells from acutely infected mice were activated in vivo and were hyperactive to the in vitro stimulation.