Document Detail

Digestive vacuole of Plasmodium falciparum released during erythrocyte rupture dually activates complement and coagulation.
MedLine Citation:
PMID:  22403252     Owner:  NLM     Status:  Publisher    
Severe P. falciparum malaria evolves through the interplay between capillaric sequestration of parasitized erythrocytes, deregulated inflammatory responses and hemostasis dysfunction. Upon rupture, each parasitized erythrocyte releases not only infective merozoites, but also the digestive vacuole (DV), a membrane-bounded organelle containing the malaria pigment hemozoin. We report that the intact organelle, but not isolated hemozoin, dually activates the alternative complement and the intrinsic clotting pathway. Pro-coagulant activity is destroyed by phospholipase C treatment, indicating a critical role of phospholipid head groups exposed at the DV surface. Intravenous injection of DVs caused alternative pathway complement consumption and provoked apathy and reduced nociceptive responses in rats. Ultrasonication destroyed complement-activating and pro-coagulant properties in vitro, and rendered the DVs biologically inactive in vivo. Low molecular weight dextran sulfate blocked activation of both complement and coagulation, and protected animals from the harmful effects of DV-infusion. We surmise that in chronic malaria, complement activation by and opsonization of the DV may subserve a useful function in directing hemozoin to phagocytic cells for safe disposal. However, when the waste disposal system of the host is overburdened, it is speculated that the DV may transform into a trigger of pathology and then represents a potential therapeutic target in severe malaria.
Prasad Dasari; Sophia D Heber; Maike Beisele; Michael Torzewski; Kurt Reifenberg; Carolin Orning; Anja Fries; Anna-Lena Zapf; Stefan Baumeister; Klaus Lingelbach; Rachanee Udomsangpetch; Sebastian Chakrit Bhakdi; Karina Reiss; Sucharit Bhakdi
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-3-8
Journal Detail:
Title:  Blood     Volume:  -     ISSN:  1528-0020     ISO Abbreviation:  -     Publication Date:  2012 Mar 
Date Detail:
Created Date:  2012-3-9     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Department of Medical Microbiology and Hygiene, University Medical Center, Johannes Gutenberg University Mainz, Germany;
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Primary medical care in the United kingdom.
Next Document:  Engagement of NKp30 on V?1 T cells induces the production of CCL3, CCL4, and CCL5 and suppresses HIV...