Abstract
The mechanisms underlying reduced red blood cell (RBC) deformability during Plasmodium falciparum (Pf) malaria remain poorly understood. Here, we explore the possible involvement of the L-arginine and nitric oxide (NO) pathway on RBC deformability in Pf-infected patients and parasite cultures. RBC deformability was reduced during the acute attack (day0) and returned to normal values upon convalescence (day28). Day0 values correlated with plasma L-arginine levels (r = 0.69; p = 0.01) and weakly with parasitemia (r = −0.38; p = 0.006). In vitro, day0 patient's plasma incubated with ring-stage cultures at 41°C reduced RBC deformability, and this effect correlated strongly with plasma L-arginine levels (r = 0.89; p < 0.0001). Moreover, addition of exogenous L-arginine to the cultures increased deformability of both Pf-free and trophozoite-harboring RBCs. NO synthase activity, evidenced in Pf-infected RBCs, induced L-arginine-dependent NO production. These data show that hypoargininemia during P. falciparum malaria may altogether impair NO production and reduce RBC deformability, particularly at febrile temperature.
Highlights
Correspondence and requests for materials should be addressed to Reduced erythrocyte deformability associated with hypoargininemia during Plasmodium falciparum malaria
Elongation index (EI, a deformability parameter) values of patient red blood cell (RBC) at day[0] were lower compared to the control group (Figure 1B), and returned to normal values 28 days after clinical recovery (Figure 1A) suggesting that the lower elongation index (EI) values of patients at day[0] were linked to malaria
Measurements in two individuals with very low parasitemia displayed the lowest EI max values. (Figure 1C; circled). These results suggest that parasitemia per se is not the sole explanatory variable for the reduced EI values of the whole RBC population of patients during malaria episodes and that uninfected RBCs (uRBCs) may be involved, confirming conclusions of studies with patients living in endemic regions[3,4]
Summary
Correspondence and requests for materials should be addressed to Reduced erythrocyte deformability associated with hypoargininemia during Plasmodium falciparum malaria. We explore the possible involvement of the L-arginine and nitric oxide (NO) pathway on RBC deformability in Pf-infected patients and parasite cultures. Day[0] patient’s plasma incubated with ring-stage cultures at 416C reduced RBC deformability, and this effect correlated strongly with plasma L-arginine levels (r 5 0.89; p , 0.0001). NO synthase activity, evidenced in Pf-infected RBCs, induced L-arginine-dependent NO production These data show that hypoargininemia during P. falciparum malaria may altogether impair NO production and reduce RBC deformability, at febrile temperature. Ecktacytometry measurements showed that whole peripheral RBCs were less deformable during acute P. falciparum malaria compared to healthy subjects[3,4] This was exacerbated in patients with severe infection, in children with severe malarial anemia, and associated with a poor prognosis[3,4]. NO has been shown to improve animal[19,20] and human[21,22,23] RBC deformability
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