title: Plasmodium falciparum avoids change in erythrocytic surface expression of phagocytosis markers during inhibition of nitric oxide synthase activity.
abstract: Nitric oxide (NO) accumulates in Plasmodium falciparum-infected erythrocytes. It may be produced by a parasite NO synthase (NOS) or by nitrate reduction. The parasite's benefit of NO accumulation is not understood. We investigated if inhibiting the P. falciparum NOS with specific and unspecific NOS inhibitors led to a decrease in intraerythrocytic NO accumulation and if this was associated with a change in surface expression of the phagocytosis markers CD47 and phosphatidyl serine. The specific inducible NOS inhibitors l-canavanine and GW274150 dose-dependently decreased intraerythrocytic NO while l-NMMA (an unspecific NOS inhibitor) and caveolin-1 scaffolding domain peptide (a specific endothelial NOS inhibitor) did not affect NO levels. Phosphatidyl serine externalization markedly increased upon P. falciparum infection. l-canavanine did not modify this whereas caveolin-1 scaffolding domain peptide increased the fraction of phosphatidyl serine exposing cells significantly. The infection did not change the level of expression of neither total CD47 nor its oxidized form. Unrelated to NOS inhibition, incubation with caveolin-1 scaffolding domain peptide lead to a decrease in oxidized CD47. In conclusion, the data imply that NOS inhibitors decrease NO accumulation in P. falciparum-infected erythrocytes but this does not correlate with the level of two major erythrocytic phagocytosis markers.
authors.affiliation: Centre for Medical Parasitology, Department for Clinical Microbiology, Copenhagen University Hospital and Department of International Health, Immunology and Microbiology, University of Copenhagen, Denmark. Electronic address: casperhempel@gmail.com.
authors.forename: Casper
authors.initials: C
authors.lastname: Hempel
authors.affiliation: Centre for Medical Parasitology, Department for Clinical Microbiology, Copenhagen University Hospital and Department of International Health, Immunology and Microbiology, University of Copenhagen, Denmark. Electronic address: kohnkehannes@gmail.com.
authors.forename: Hannes
authors.initials: H
authors.lastname: Kohnke
authors.affiliation: Centre for Medical Parasitology, Department for Clinical Microbiology, Copenhagen University Hospital and Department of International Health, Immunology and Microbiology, University of Copenhagen, Denmark. Electronic address: lassemaretty@gmail.com.
authors.forename: Lasse
authors.initials: L
authors.lastname: Maretty
authors.affiliation: Department for Clinical Microbiology, Copenhagen University Hospital, Copenhagen, Denmark. Electronic address: peter.oestrup.jensen@regionh.dk.
authors.forename: Peter Ø
authors.initials: PØ
authors.lastname: Jensen
authors.affiliation: Centre for Medical Parasitology, Department for Clinical Microbiology, Copenhagen University Hospital and Department of International Health, Immunology and Microbiology, University of Copenhagen, Denmark. Electronic address: staalsoe@cmp.dk.
authors.forename: Trine
authors.initials: T
authors.lastname: Staalsø
authors.affiliation: Centre for Medical Parasitology, Department for Clinical Microbiology, Copenhagen University Hospital and Department of International Health, Immunology and Microbiology, University of Copenhagen, Denmark. Electronic address: joergen.kurtzhals@regionh.dk.
authors.forename: Jørgen A L
authors.initials: JA
authors.lastname: Kurtzhals
mesh_terms: D000941:Antigens / Q000235:genetics* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004912:Erythrocytes / Q000378:metabolism / Q000469:parasitology*; D006790:Host-Parasite Interactions; D006801:Humans; D016778:Malaria, Falciparum / Q000235:genetics / Q000378:metabolism / Q000469:parasitology* / Q000503:physiopathology; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D010587:Phagocytosis / Q000187:drug effects; D010963:Plasmodium falciparum / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D015800:Protozoan Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D000941:Antigens; C042182:D47 antigen; D004791:Enzyme Inhibitors; D015800:Protozoan Proteins; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase
keywords: Nitric oxide; Nitric oxide synthase; Phagocytosis; Plasmodium falciparum