title: Platelet apoptosis and apoptotic platelet clearance by macrophages in secondary dengue virus infections.
abstract: BACKGROUND
  The mechanisms of thrombocytopenia and platelet phagocytosis in dengue illness are not fully understood.
  
  
  METHODS
  A prospective hospital-based study was conducted to examine the relationships between platelet counts, serum thrombopoietin (TPO) levels, and platelet apoptosis and phagocytosis in 81 patients with secondary dengue virus (DV) infections and 38 healthy volunteers. The apoptosis and phagocytosis of cultured platelets after exposure to DV were also examined.
  
  
  RESULTS
  Platelet apoptosis, platelet phagocytosis, and serum TPO levels were increased significantly in patients during the acute and early convalescence phases compared with levels observed in patients during the convalescence phase and in healthy volunteers. A significant correlation between platelet apoptosis and platelet phagocytosis was also observed in these patients. Platelet phagocytosis was inhibited significantly by the D89E mutant, which carries a point mutation in the RGD motif of milk fat globule-epidermal growth factor 8, a phosphatidylserine-recognizing bridge molecule. DV-induced platelet apoptosis and increased phagocytosis of DV-induced apoptotic platelets was confirmed using in vitro assays.
  
  
  CONCLUSIONS
  Our data suggest an increased phagocytosis of DV-induced apoptotic platelets by macrophages via a phosphatidylserine-recognizing pathway in secondary DV infection. Accelerated platelet clearance, however, was overcome by TPO-induced enhanced thrombopoiesis in these patients.
  
  
  BACKGROUND
  UMIN000004835.
authors.affiliation: Laboratory for Clinical Research on Infectious Diseases, International Research Center for Infectious Diseases, Osaka University, Japan.
authors.forename: Maria Terrese G
authors.initials: MT
authors.lastname: Alonzo
authors.forename: Talitha Lea V
authors.initials: TL
authors.lastname: Lacuesta
authors.forename: Efren M
authors.initials: EM
authors.lastname: Dimaano
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kurosu
authors.forename: Lady-Anne C
authors.initials: LA
authors.lastname: Suarez
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Mapua
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Akeda
authors.forename: Ronald R
authors.initials: RR
authors.lastname: Matias
authors.forename: David J
authors.initials: DJ
authors.lastname: Kuter
authors.forename: Shigekazu
authors.initials: S
authors.lastname: Nagata
authors.forename: Filipinas F
authors.initials: FF
authors.lastname: Natividad
authors.forename: Kazunori
authors.initials: K
authors.lastname: Oishi
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000502:physiology*; D001792:Blood Platelets / Q000166:cytology* / Q000502:physiology; D016022:Case-Control Studies; D003715:Dengue / Q000473:pathology*; D006801:Humans; D008264:Macrophages / Q000502:physiology*; D010976:Platelet Count; D013926:Thrombopoietin; D055815:Young Adult
chemical_list: D013926:Thrombopoietin