Marked elevation in plasma osteoprotegerin constitutes an early and consistent feature of cerebral malaria

Thrombosis and Haemostasis
Niamh O'ReganJames O'Donnell

Abstract

Adherence of infected erythrocytes to vascular endothelium causes acute endothelial cell (EC) activation during Plasmodium falciparum infection. Consequently, proteins stored in Weibel-Palade (WP) bodies within EC are secreted into the plasma. Osteoprotegerin (OPG) binds to VWF and consequently is stored within WP bodies. Given the critical role of EC activation in the pathogenesis of severe malaria, we investigated plasma OPG levels in children with P. falciparum malaria. At presentation, plasma OPG levels were significantly elevated in children with cerebral malaria (CM) compared to healthy controls (means 16.0 vs 0.8 ng/ml; p< 0.01). Importantly, OPG levels were also significantly higher in children with CM who had a fatal outcome, compared to children with CM who survived. Finally, in children with CM, plasma OPG levels correlated with other established prognostic indices (including plasma lactate levels and peripheral parasite density). To further investigate the relationship between severe malaria and OPG, we utilised a murine model of experimental CM in which C57BL/6J mice were infected with P. berghei ANKA. Interestingly, plasma OPG levels were increased 4.6 fold within 24 hours following P. berghei inoculation. This ea...Continue Reading

References

Jun 15, 1989·The New England Journal of Medicine·G E GrauP H Lambert
Jan 1, 1994·Transactions of the Royal Society of Tropical Medicine and Hygiene·S KrishnaP A Holloway
Mar 23, 2002·Microbes and Infection·J Brian de Souza, Eleanor M Riley
Sep 3, 2005·Nature Reviews. Immunology·Louis Schofield, Georges E Grau
May 10, 2006·British Journal of Haematology·Martine J HollestelleJames Bunn
Jun 30, 2007·The American Journal of Pathology·Fiona H AmanteChristian R Engwerda
Jul 13, 2007·The Journal of Infectious Diseases·Quirijn de MastAndre van der Ven
Aug 29, 2007·Journal of Thrombosis and Haemostasis : JTH·S ShahbaziO D Christophe
Jun 7, 2008·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Arjen M DondorpNicholas J White
Oct 30, 2008·Proceedings of the National Academy of Sciences of the United States of America·Tsin W YeoNicholas M Anstey
Jan 12, 2010·Thrombosis and Haemostasis·Ester C LöwenbergArjen M Dondorp
Aug 20, 2010·Arteriosclerosis, Thrombosis, and Vascular Biology·Kenneth CaidahlPål Aukrust
Jan 27, 2011·Blood·Karine M ValentijnJeroen Eikenboom
Jul 17, 2013·Journal of Thrombosis and Haemostasis : JTH·T Nightingale, D Cutler
Jul 6, 2013·Cytokine & Growth Factor Reviews·Marc Baud'huinDominique Heymann
Sep 21, 2013·The Journal of Infectious Diseases·Christopher A MoxonRobert S Heyderman
Mar 19, 2015·The New England Journal of Medicine·Karl B SeydelTerrie E Taylor

❮ Previous
Next ❯

Methods Mentioned

BETA
enzyme-linked immunosorbent assay
ELISAs

Software Mentioned

Graphpad Prism
GraphPad

Related Concepts

Related Feeds

Antimalarial Agents (ASM)

Antimalarial agents, also known as antimalarials, are designed to prevent or cure malaria. Discover the latest research on antimalarial agents here.

Antimalarial Agents

Antimalarial agents, also known as antimalarials, are designed to prevent or cure malaria. Discover the latest research on antimalarial agents here.