Platelet Apoptosis and Apoptotic Platelet Clearance by Macrophages in Secondary Dengue Virus Infections

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 phagocyto...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of infectious diseases 2012-04, Vol.205 (8), p.1321-1329
Main Authors: Alonzo, Maria Terrese G., Lacuesta, Talitha Lea V., Dimaano, Efren M., Kurosu, Takeshi, Suarez, Lady-anne C., Mapua, Cynthia A., Akeda, Yukihiro, Matias, Ronald R., Kuter, David J., Nagata, Shigekazu, Natividad, Filipinas F., Oishi, Kazunori
Format: Article
Language:English
Subjects:
Adult
Annexins
Apoptosis
Apoptosis - physiology
Arboviroses
Biological and medical sciences
Blood
Blood Platelets - cytology
Blood Platelets - physiology
Case-Control Studies
Convalescence
Dengue
Dengue - pathology
Dengue fevers
Dengue virus
Fundamental and applied biological sciences. Psychology
Human viral diseases
Humans
Infections
Infectious diseases
Macrophages - physiology
Medical sciences
Microbiology
Phagocytosis
Platelet Count
Platelets
Pretreatment
Thrombopoietin
Tropical viral diseases
Viral diseases
VIRUSES
Young Adult
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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. Clinical Trials Registration. UMIN000004835.
ISSN:0022-1899
1537-6613
DOI:10.1093/infdis/jis180