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Title: Digestive vacuole of Plasmodium falciparum released during erythrocyte rupture dually activates complement and coagulation
Authors: 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
Johannes Gutenberg Universitat Mainz
Robert Bosch Krankenhaus Stuttgart
Universitat Marburg
Mahidol University
Christian-Albrechts-Universitat zu Kiel
Keywords: Biochemistry, Genetics and Molecular Biology;Immunology and Microbiology;Medicine
Issue Date: 3-May-2012
Citation: Blood. Vol.119, No.18 (2012), 4301-4310
Abstract: Severe Plasmodium falciparum malaria evolves through the interplay among capillary sequestration of parasitized erythrocytes, deregulated inflammatory responses, and hemostasis dysfunction. After rupture, each parasitized erythrocyte releases not only infective merozoites, but also the digestive vacuole (DV), a membrane-bounded organelle containing the malaria pigment hemozoin. In the present study, we report that the intact organelle, but not isolated hemozoin, dually activates the alternative complement and the intrinsic clotting pathway. Procoagulant 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 procoagulant properties in vitro and rendered the DVs biologically inactive in vivo. Lowmolecular- 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 serve a useful function in directing hemozoin to phagocytic cells for safe disposal. However, when the waste disposal system of the host is overburdened, DVs may transform into a trigger of pathology and therefore represent a potential therapeutic target in severe malaria. © 2012 by The American Society of Hematology.
ISSN: 15280020
Appears in Collections:Scopus 2011-2015

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