Reduced erythrocyte deformability associated with hypoargininemia during Plasmodium falciparum malaria.
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.
1] Institut Pasteur, Immunologie Moléculaire des Parasites, Département de Parasitologie Mycologie, F- 75015 Paris, France [2] CNRS, URA2581, F- 75015 Paris, France.
Juliana
J
Rey
1] INSERM - UPMC (Paris 6 University) UMRs945, F-75013 Paris, France [2] AP-HP, Department of Parasitology, Pitié Salpétrière Hospital, F-75013 Paris, France.
Pierre A
PA
Buffet
1] INSERM - UPMC (Paris 6 University) UMRs945, F-75013 Paris, France [2] AP-HP, Department of Parasitology, Pitié Salpétrière Hospital, F-75013 Paris, France.
Liliane
L
Ciceron
Institut Pasteur, Immunophysiologie et Parasitisme, Département de Parasitologie Mycologie, F-75015 Paris, France.
Geneviève
G
Milon
1] Institut Pasteur, Immunologie Moléculaire des Parasites, Département de Parasitologie Mycologie, F- 75015 Paris, France [2] CNRS, URA2581, F- 75015 Paris, France.
Odile
O
Mercereau-Puijalon
1] Institut Pasteur, Immunologie Moléculaire des Parasites, Département de Parasitologie Mycologie, F- 75015 Paris, France [2] CNRS, URA2581, F- 75015 Paris, France [3] Center for Rare and Neglected Diseases, and Department of Biological Sciences, University of Notre Dame, Notre Dame, Indiana, USA.
Innocent
I
Safeukui
D000328:Adult; D001120:Arginine / Q000097:blood* / Q000172:deficiency / Q000378:metabolism; D004907:Erythrocyte Deformability; D004912:Erythrocytes / Q000473:pathology*; D005260:Female; D006801:Humans; D016778:Malaria, Falciparum / Q000097:blood* / Q000209:etiology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000097:blood; D010963:Plasmodium falciparum / Q000378:metabolism / Q000472:pathogenicity; D013696:Temperature
D009569:Nitric Oxide; D001120:Arginine