Red Blood Cells Preconditioned with Hemin Are Less Permissive to Plasmodium Invasion In Vivo and In Vitro

Abstract

Malaria is a parasitic disease that causes severe hemolytic anemia in Plasmodium-infected hosts, which results in the release and accumulation of oxidized heme (hemin). Although hemin impairs the establishment of Plasmodium immunity in vitro and in vivo, mice preconditioned with hemin develop lower parasitemia when challenged with Plasmodium chabaudi adami blood stage parasites. In order to understand the mechanism accounting for this resistance as well as the impact of hemin on eryptosis and plasma levels of scavenging hemopexin, red blood cells were labeled with biotin prior to hemin treatment and P. c. adami infection. This strategy allowed discriminating hemin-treated from de novo generated red blood cells and to follow the infection within these two populations of cells. Fluorescence microscopy analysis of biotinylated-red blood cells revealed increased P. c. adami red blood cells selectivity and a decreased permissibility of hemin-conditioned red blood cells for parasite invasion. These effects were also apparent in in vitro P. falciparum cultures using hemin-preconditioned human red blood cells. Interestingly, hemin did not alter the turnover of red blood cells nor their replenishment during in vivo infection. Our results assign a function for hemin as a protective agent against high parasitemia, and suggest that the hemolytic nature of blood stage human malaria may be beneficial for the infected host.

Alterations in Systemic Extracellular Heme and Hemopexin Are Associated With Adverse Clinical Outcomes in Ugandan Children With Severe Malaria

“…This contention is supported by Dalko et al, who observed a significant positive correlation between heme and parasite burden, as measured by HRP-2 levels [ 18 ]. Conversely, there is evidence that extracellular heme may limit the permissibility of red blood cells to merozoite invasion, thereby leading to lower parasitemia counts in both in vitro culture and in vivo mouse models [ 25 ]. This may also explain, at least partly, the association between severe malarial anemia and lower parasite burdens [ 21 , 26 ].…”

Modulation of Redox Signaling and Thiol Homeostasis in Red Blood Cells by Peroxiredoxin Mimetics

“…Confocal images were acquired with a Leica TCS SP8 fluorescence microscope and were further analyzed and extracted using LAS X (Leica) software. 62 Expression and Purification of Thioredoxin (Trx). E. coli BL21(DE3) cells were transformed with pJK615 (Addgene Plasmid #71699, produces E. coli Trx with a C-terminal His6 tag), individual colonies were inoculated in L.B.…”

“…Differential interference contrast (DIC) images were taken to analyze the morphological changes in RBCs. Confocal images were acquired with a Leica TCS SP8 fluorescence microscope and were further analyzed and extracted using LAS X (Leica) software …”

Suicidal death of erythrocytes in cancer and its chemotherapy: A potential target in the treatment of tumor‐associated anemia

“…The eryptosis in malignancy is stimulated, at least in part, by a plasma component. The percentage of eryptotic erythrocytes was significantly higher following exposure of healthy 10,11 Hepatic injury 12,13 Cardiac failure 14 Chronic kidney disease [15][16][17][18] Hemolytic uremic syndrome 1 Dehydration 19 Phosphate depletion 1 Calcitriol excess 20 Inflammation 21 Arteritis 22 Fever 23 Sepsis 24 Systemic lupus erythematosus 25 Mycoplasma infection 1 Malaria [26][27][28] Iron deficiency 29 Sickle cell anemia 30 Thalassemia 30 Glucose 6-phosphate dehydrogenase deficiency 31,32 Hereditary spherocytosis 2,23 Paroxysmal nocturnal haemoglobinuria 1 Wilsons disease 1 Parkinsons disease 33 Malignancy (see text).…”