| Complement receptor 1 is a sialic acid-independent erythrocyte receptor of Plasmodium falciparum. | |
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MedLine Citation:
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PMID: 20585558 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Plasmodium falciparum is a highly lethal malaria parasite of humans. A major portion of its life cycle is dedicated to invading and multiplying inside erythrocytes. The molecular mechanisms of erythrocyte invasion are incompletely understood. P. falciparum depends heavily on sialic acid present on glycophorins to invade erythrocytes. However, a significant proportion of laboratory and field isolates are also able to invade erythrocytes in a sialic acid-independent manner. The identity of the erythrocyte sialic acid-independent receptor has been a mystery for decades. We report here that the complement receptor 1 (CR1) is a sialic acid-independent receptor for the invasion of erythrocytes by P. falciparum. We show that soluble CR1 (sCR1) as well as polyclonal and monoclonal antibodies against CR1 inhibit sialic acid-independent invasion in a variety of laboratory strains and wild isolates, and that merozoites interact directly with CR1 on the erythrocyte surface and with sCR1-coated microspheres. Also, the invasion of neuraminidase-treated erythrocytes correlates with the level of CR1 expression. Finally, both sialic acid-independent and dependent strains invade CR1 transgenic mouse erythrocytes preferentially over wild-type erythrocytes but invasion by the latter is more sensitive to neuraminidase. These results suggest that both sialic acid-dependent and independent strains interact with CR1 in the normal red cell during the invasion process. However, only sialic acid-independent strains can do so without the presence of glycophorin sialic acid. Our results close a longstanding and important gap in the understanding of the mechanism of erythrocyte invasion by P. falciparum that will eventually make possible the development of an effective blood stage vaccine. |
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Authors:
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Carmenza Spadafora; Gordon A Awandare; Karen M Kopydlowski; Jozsef Czege; J Kathleen Moch; Robert W Finberg; George C Tsokos; José A Stoute |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. Date: 2010-06-17 |
Journal Detail:
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Title: PLoS pathogens Volume: 6 ISSN: 1553-7374 ISO Abbreviation: PLoS Pathog. Publication Date: 2010 |
Date Detail:
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Created Date: 2010-06-29 Completed Date: 2010-10-27 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101238921 Medline TA: PLoS Pathog Country: United States |
Other Details:
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Languages: eng Pagination: e1000968 Citation Subset: IM |
Affiliation:
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Department of Medicine, the Uniformed Services University of the Health Sciences, Bethesda, Maryland, United States of America. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Blotting, Western Erythrocytes / metabolism*, parasitology* Flow Cytometry Fluorescent Antibody Technique Humans Immunoprecipitation Malaria, Falciparum / metabolism*, virology Membrane Glycoproteins / metabolism* Merozoites / physiology Mice Mice, Inbred C57BL Mice, Transgenic N-Acetylneuraminic Acid / metabolism* Plasmodium falciparum / physiology* Receptors, Complement / metabolism* Receptors, Immunologic / metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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D43 TW06239/TW/FIC NIH HHS; HL 71502/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Membrane Glycoproteins; 0/Receptors, Complement; 0/Receptors, Immunologic; 0/erythrocyte receptor; 131-48-6/N-Acetylneuraminic Acid |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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