title: Plasmodium falciparum, but not P. vivax, can induce erythrocytic apoptosis.
abstract: BACKGROUND
  Apoptosis can occur in red blood cells (RBC) and seems to be involved in hematologic disorders related to many diseases. In malaria it is known that parasitized RBC (pRBC) is involved in the development of anemia and thrombosis; however, non-parasitized RBC (nRBC) apoptosis could amplify these malaria-associated hematologic events. In fact, in experimental malaria, increased levels of apoptosis were observed in nRBC during lethal Plasmodium yoelii 17XL infection, but in human malaria erythrocytic apoptosis has never been studied. The present study was performed to investigate if nRBC apoptosis also occurs in P. vivax and P. falciparum infections.
  
  
  RESULTS
  Apoptosis of nRBC was evaluated in blood samples of P. vivax malaria patients and clinically healthly individuals living in Manaus, Brazil, both ex vivo and after incubation of RBC for 24 h. Additionally, the capacity of plasma from P. vivax or P. falciparum patients was tested for induction of in vitro apoptosis of normal RBC from a clinically healthy individual living in a non-endemic malaria region. Apoptosis was detected by flow cytometry using annexin V staining. In contrast to experimental malaria that significantly increased the levels of apoptotic nRBC both ex-vivo and after 24 h of incubation, no significant alteration on apoptotic nRBC rates was detected in P. vivax infected patients when compared with non-infected control individuals. Similar results were observed when plasma of these P. vivax patients was incubated with normal RBC. Conversely, plasma from P. falciparum-infected subjects induced significant apoptosis of these cells.
  
  
  CONCLUSIONS
  Apoptosis of normal RBC can be induced by plasma from individuals with P. falciparum (but not with P. vivax) malaria. This finding could reflect the existence of erythrocytic apoptosis during infection that could contribute to the pathogenesis of hematological and vascular complications associated with falciparum malaria.
authors.affiliation: Laboratório de Pesquisas em Malária, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, Brazil. prtotino@ioc.fiocruz.br.|Centro de Pesquisa, Diagnóstico e Treinamento em Malária, Secretaria de Vigilância em Saúde, Ministério da Saúde, Brazil. prtotino@ioc.fiocruz.br.
authors.forename: Paulo Renato Rivas
authors.initials: PR
authors.lastname: Totino
authors.affiliation: Laboratório de Pesquisas em Malária, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, Brazil. das.magalhaes@bol.com.br.|Centro de Pesquisa, Diagnóstico e Treinamento em Malária, Secretaria de Vigilância em Saúde, Ministério da Saúde, Brazil. das.magalhaes@bol.com.br.
authors.forename: Aline das Dores
authors.initials: Ad
authors.lastname: Magalhães
authors.affiliation: Fundação de Hematologia e Hemoterapia do Amazonas, Manaus, Brazil. eliana.brasil@hemoam.am.gov.br.
authors.forename: Eliana Brasil
authors.initials: EB
authors.lastname: Alves
authors.affiliation: Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, Brazil. mcmanso@fmt.am.gov.br.
authors.forename: Monica Regina Farias
authors.initials: MR
authors.lastname: Costa
authors.affiliation: Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, Brazil. marcuslacerda.br@gmail.com.
authors.forename: Marcus Vinícius Guimarães
authors.initials: MV
authors.lastname: de Lacerda
authors.affiliation: Laboratório de Pesquisas em Malária, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, Brazil. ribeiro@ioc.fiocruz.br.|Centro de Pesquisa, Diagnóstico e Treinamento em Malária, Secretaria de Vigilância em Saúde, Ministério da Saúde, Brazil. ribeiro@ioc.fiocruz.br.
authors.forename: Cláudio Tadeu
authors.initials: CT
authors.lastname: Daniel-Ribeiro
authors.affiliation: Laboratório de Pesquisas em Malária, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, Brazil. mffcruz@ioc.fiocruz.br.|Centro de Pesquisa, Diagnóstico e Treinamento em Malária, Secretaria de Vigilância em Saúde, Ministério da Saúde, Brazil. mffcruz@ioc.fiocruz.br.
authors.forename: Maria de Fátima
authors.initials: Mde F
authors.lastname: Ferreira-da-Cruz
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D004912:Erythrocytes / Q000469:parasitology* / Q000502:physiology; D006801:Humans; D016778:Malaria, Falciparum / Q000469:parasitology*; D016780:Malaria, Vivax / Q000469:parasitology*; D018512:Parasitemia; D010963:Plasmodium falciparum / Q000502:physiology*; D010966:Plasmodium vivax / Q000502:physiology*