The killing of blood-stage
malaria parasites in vivo has been attributed to reactive intermediates of
oxygen (ROI) and of
nitrogen (RNI). However, in the case of the latter, this contention is challenged by recent observations that
parasitemia was not exacerbated in
nitric oxide synthase (NOS) knockout (KO) (NOS2-/- or NOS3-/-) mice or in mice treated with NOS inhibitors. We now report that the time course shows that Plasmodium chabaudi
parasitemia in
NADPH oxidase KO (p47phox-/-) mice also was not exacerbated, suggesting a minimal role for ROI-mediated killing of blood-stage parasites. It is possible that the production of protective
antibodies during
malaria may mask the function of ROI and/or RNI. However,
parasitemia in B-cell-deficient JH-/- x NOS2-/- or JH-/- x p47phox-/- mice was not exacerbated. In contrast, the magnitude of peak
parasitemia was significantly enhanced in p47phox-/- mice treated with the
xanthine oxidase inhibitor
allopurinol, but the duration of patent
parasitemia was not prolonged. Whereas the time course of
parasitemia in NOS2-/- x p47phox-/- mice was nearly identical to that seen in normal control mice,
allopurinol treatment of these double-KO mice also enhanced the magnitude of peak
parasitemia. Thus, ROI generated via the
xanthine oxidase pathway contribute to the control of ascending P. chabaudi
parasitemia during
acute malaria but alone are insufficient to suppress
parasitemia to subpatent levels. Together, these results indicate that ROI or RNI can contribute to, but are not essential for, the suppression of
parasitemia during blood-stage
malaria.