title: Accelerated senescence of human erythrocytes cultured with Plasmodium falciparum.
abstract: Red blood cells infected withPlasmodium falciparum(IRBCs) undergo changes primarily in their membrane composition that contribute to malaria pathogenesis. However, all manifestations (eg, anemia) cannot be accounted for by IRBCs alone. Uninfected erythrocytes (URBCs) may play a role, but they have been under-researched. We wanted to document changes in the erythrocyte membrane that could contribute to URBC reduced life span and malaria-associated anemia. Human erythrocytes were cultured withP falciparumand washed at the trophozoite stage. IRBCs and URBCs were separated on Percoll density gradient, thus obtaining erythrocyte fractions of different densities/ages. IRBC- and URBC-purified membranes were analyzed and compared with control normal erythrocytes (NRBCs) of the same age, from the same donor, kept in the same conditions.P falciparumaccelerated aging of both IRBCs and URBCs, causing a significant shift in the cell population toward the denser (old) fraction. Protein, phospholipid, and cholesterol content were reduced in IRBCs and young URBCs. Young and medium uninfected fractions had higher levels of lipid peroxidation and phospholipid saturation (because of the loss of polyunsaturated fatty acids, PUFAs) and lower phosphatidylserine. In IRBCs, thiobarbituric reactive substances (TBARSs) were higher, and PUFAs and phosphatidylserine lower than in NRBCs and URBCs. In comparison, trophozoite membranes had lower phospholipid (particularly sphingomyelin and phosphatidylserine) and cholesterol content and a higher degree of saturation. Parasite-induced peroxidative damage might account for these modifications. In summary, we demonstrated that membrane damage leading to accelerated senescence of both infected and uninfected erythrocytes will likely contribute to malaria anemia.
authors.affiliation: Istituto di Fisiologia Generale e Chimica Biologica Giovanni Esposito, Facoltà di Farmacia, Via Trentacoste 2, 20134-Milano, Italy. omodeo@mailserver.unimi.it
authors.forename: Fausta
authors.initials: F
authors.lastname: Omodeo-Salè
authors.forename: Anna
authors.initials: A
authors.lastname: Motti
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Basilico
authors.forename: Silvia
authors.initials: S
authors.lastname: Parapini
authors.forename: Piero
authors.initials: P
authors.lastname: Olliaro
authors.forename: Donatella
authors.initials: D
authors.lastname: Taramelli
mesh_terms: D000818:Animals; D024201:Bystander Effect; D002784:Cholesterol / Q000032:analysis; D018920:Coculture Techniques; D004905:Erythrocyte Aging; D004910:Erythrocyte Membrane / Q000737:chemistry / Q000648:ultrastructure; D004912:Erythrocytes / Q000737:chemistry / Q000469:parasitology*; D005227:Fatty Acids / Q000032:analysis; D005231:Fatty Acids, Unsaturated / Q000032:analysis; D006801:Humans; D015227:Lipid Peroxidation; D008563:Membrane Lipids / Q000032:analysis; D008565:Membrane Proteins / Q000032:analysis; D018384:Oxidative Stress; D010743:Phospholipids / Q000032:analysis; D010963:Plasmodium falciparum / Q000737:chemistry / Q000254:growth & development / Q000502:physiology*; D015800:Protozoan Proteins / Q000032:analysis; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis
chemical_list: D005227:Fatty Acids; D005231:Fatty Acids, Unsaturated; D008563:Membrane Lipids; D008565:Membrane Proteins; D010743:Phospholipids; D015800:Protozoan Proteins; D017392:Thiobarbituric Acid Reactive Substances; D002784:Cholesterol