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Production, fate and pathogenicity of plasma microparticles in murine cerebral malaria

El-Assaad, Fatima ; Wheway, Julie ; Hunt, Nicholas H ; Grau, Georges E R ; Combes, Valery Frevert, Ute

PLoS pathogens, 2014-03, Vol.10 (3), p.e1003839-e1003839 [Periódico revisado por pares]

United States: Public Library of Science

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Título:
Production, fate and pathogenicity of plasma microparticles in murine cerebral malaria
Autor: El-Assaad, Fatima ; Wheway, Julie ; Hunt, Nicholas H ; Grau, Georges E R ; Combes, Valery
Frevert, Ute
Assuntos: Adoptive Transfer ; Animals ; Antigens ; Brain research ; Cell membranes ; Cell-Derived Microparticles - pathology ; Disease Models, Animal ; Female ; Flow Cytometry ; Fluorescent Antibody Technique ; Health aspects ; Homeostasis ; Host-parasite relationships ; Infections ; Malaria ; Malaria, Cerebral - blood ; Medical research ; Medicine ; Mice ; Mice, Inbred CBA ; Microbiological research ; Nanoparticles ; Neurological research ; Pathogenesis ; Physiological aspects ; Plasma ; Plasmodium ; Plasmodium berghei - pathogenicity ; Rodents ; Variance analysis ; Virulence
É parte de: PLoS pathogens, 2014-03, Vol.10 (3), p.e1003839-e1003839
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
The authors have declared that no competing interests exist.
Conceived and designed the experiments: FE GERG VC JW NHH. Performed the experiments: FE JW. Analyzed the data: FE GERG VC. Contributed reagents/materials/analysis tools: NHH. Wrote the paper: FE.
Descrição: In patients with cerebral malaria (CM), higher levels of cell-specific microparticles (MP) correlate with the presence of neurological symptoms. MP are submicron plasma membrane-derived vesicles that express antigens of their cell of origin and phosphatidylserine (PS) on their surface, facilitating their role in coagulation, inflammation and cell adhesion. In this study, the in vivo production, fate and pathogenicity of cell-specific MP during Plasmodium berghei infection of mice were evaluated. Using annexin V, a PS ligand, and flow cytometry, analysis of platelet-free plasma from infected mice with cerebral involvement showed a peak of MP levels at the time of the neurological onset. Phenotypic analyses showed that MP from infected mice were predominantly of platelet, endothelial and erythrocytic origins. To determine the in vivo fate of MP, we adoptively transferred fluorescently labelled MP from mice with CM into healthy or infected recipient mice. MP were quickly cleared following intravenous injection, but microscopic examination revealed arrested MP lining the endothelium of brain vessels of infected, but not healthy, recipient mice. To determine the pathogenicity of MP, we transferred MP from activated endothelial cells into healthy recipient mice and this induced CM-like brain and lung pathology. This study supports a pathogenic role for MP in the aggravation of the neurological lesion and suggests a causal relationship between MP and the development of CM.
Editor: United States: Public Library of Science
Idioma: Inglês

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Production, fate and pathogenicity of plasma microparticles in murine cerebral malaria

El-Assaad, Fatima ; Wheway, Julie ; Hunt, Nicholas H ; Grau, Georges E R ; Combes, Valery Frevert, Ute

United States: Public Library of Science

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