Publication: Digestive vacuole of Plasmodium falciparum released during erythrocyte rupture dually activates complement and coagulation
Issued Date
2012-05-03
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ISSN
15280020
00064971
00064971
Other identifier(s)
2-s2.0-84860736934
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Mahidol University
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SCOPUS
Bibliographic Citation
Blood. Vol.119, No.18 (2012), 4301-4310
Suggested Citation
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 Digestive vacuole of Plasmodium falciparum released during erythrocyte rupture dually activates complement and coagulation. Blood. Vol.119, No.18 (2012), 4301-4310. doi:10.1182/blood-2011-11-392134 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/13735
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Title
Digestive vacuole of Plasmodium falciparum released during erythrocyte rupture dually activates complement and coagulation
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.