Study of platelet-mediated clumping adhesion phenotypes in Plasmodium falciparum malaria
<p>Platelet-mediated clumping of <em>Plasmodium falciparum</em>-infected erythrocytes (IEs) is a common property of field isolates associated with severe disease (Pain, Ferguson <em>et al</em>. 2001). Platelet receptors CD36 (Pain, Ferguson <em>et al</em>. 2...
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| Format: | Disertacija |
| Jezik: | English |
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2015
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| _version_ | 1826316143367815168 |
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| author | Onyambu, F Frank Onyambu |
| author2 | Roberts, D |
| author_facet | Roberts, D Onyambu, F Frank Onyambu |
| author_sort | Onyambu, F |
| collection | OXFORD |
| description | <p>Platelet-mediated clumping of <em>Plasmodium falciparum</em>-infected erythrocytes (IEs) is a common property of field isolates associated with severe disease (Pain, Ferguson <em>et al</em>. 2001). Platelet receptors CD36 (Pain, Ferguson <em>et al</em>. 2001), P-Selectin (Wassmer, Taylor <em>et al</em>. 2008) and gC1qR (Biswas, Hafiz <em>et al</em>. 2007) mediate clumping. To characterize the molecular specificities of the clumping phenotype, I cloned clumping parasite line IT/C10 by limiting dilution. I characterized <em>var</em> gene expression in the IT/C10 clones using generic primers for the DBL tag region (Bull, Berriman <em>et al</em>. 2005). Clumping assays were conducted in the presence of specific reagents to delineate host factors hypothesized to contribute to development of the clumping phenotype. Finally, I conducted a clinical study with isolates from children with malaria in Kilifi, Kenya.</p> <p>This study shows that in parasite line IT/C10, platelet-mediated clumping is associated with Itvar30 suggesting a prominent role for the PfEMP-1 encoded by this <em>var</em> gene in development of platelet-mediated clumping. For IT/C10 parasites, platelet activation appears to be involved in platelet-mediated clumping. Platelet P-Selectin appears to mediate clumping using lectin-dependent interactions. To further elucidate the mechanisms that mediate clumping by host platelets, I have used a panel of platelet antagonists to delineate specific platelet activation pathways. Our results show that platelet activation plays an important role in platelet-mediated clumping. Finally, in this study, platelet-mediated clumping was associated with parasitaemia, but not with disease severity.</p> |
| first_indexed | 2024-03-06T20:14:47Z |
| format | Thesis |
| id | oxford-uuid:2bc489a9-121e-41ab-8830-1cb07e5b01f2 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-12-09T03:38:34Z |
| publishDate | 2015 |
| record_format | dspace |
| spelling | oxford-uuid:2bc489a9-121e-41ab-8830-1cb07e5b01f22024-12-07T10:11:49ZStudy of platelet-mediated clumping adhesion phenotypes in Plasmodium falciparum malariaThesishttp://purl.org/coar/resource_type/c_db06uuid:2bc489a9-121e-41ab-8830-1cb07e5b01f2HaematologyClinical laboratory sciencesMedical sciencesInfectious diseasesMalariaEnglishOxford University Research Archive - Valet2015Onyambu, FFrank OnyambuRoberts, DBull, P<p>Platelet-mediated clumping of <em>Plasmodium falciparum</em>-infected erythrocytes (IEs) is a common property of field isolates associated with severe disease (Pain, Ferguson <em>et al</em>. 2001). Platelet receptors CD36 (Pain, Ferguson <em>et al</em>. 2001), P-Selectin (Wassmer, Taylor <em>et al</em>. 2008) and gC1qR (Biswas, Hafiz <em>et al</em>. 2007) mediate clumping. To characterize the molecular specificities of the clumping phenotype, I cloned clumping parasite line IT/C10 by limiting dilution. I characterized <em>var</em> gene expression in the IT/C10 clones using generic primers for the DBL tag region (Bull, Berriman <em>et al</em>. 2005). Clumping assays were conducted in the presence of specific reagents to delineate host factors hypothesized to contribute to development of the clumping phenotype. Finally, I conducted a clinical study with isolates from children with malaria in Kilifi, Kenya.</p> <p>This study shows that in parasite line IT/C10, platelet-mediated clumping is associated with Itvar30 suggesting a prominent role for the PfEMP-1 encoded by this <em>var</em> gene in development of platelet-mediated clumping. For IT/C10 parasites, platelet activation appears to be involved in platelet-mediated clumping. Platelet P-Selectin appears to mediate clumping using lectin-dependent interactions. To further elucidate the mechanisms that mediate clumping by host platelets, I have used a panel of platelet antagonists to delineate specific platelet activation pathways. Our results show that platelet activation plays an important role in platelet-mediated clumping. Finally, in this study, platelet-mediated clumping was associated with parasitaemia, but not with disease severity.</p> |
| spellingShingle | Haematology Clinical laboratory sciences Medical sciences Infectious diseases Malaria Onyambu, F Frank Onyambu Study of platelet-mediated clumping adhesion phenotypes in Plasmodium falciparum malaria |
| title | Study of platelet-mediated clumping adhesion phenotypes in Plasmodium falciparum malaria |
| title_full | Study of platelet-mediated clumping adhesion phenotypes in Plasmodium falciparum malaria |
| title_fullStr | Study of platelet-mediated clumping adhesion phenotypes in Plasmodium falciparum malaria |
| title_full_unstemmed | Study of platelet-mediated clumping adhesion phenotypes in Plasmodium falciparum malaria |
| title_short | Study of platelet-mediated clumping adhesion phenotypes in Plasmodium falciparum malaria |
| title_sort | study of platelet mediated clumping adhesion phenotypes in plasmodium falciparum malaria |
| topic | Haematology Clinical laboratory sciences Medical sciences Infectious diseases Malaria |
| work_keys_str_mv | AT onyambuf studyofplateletmediatedclumpingadhesionphenotypesinplasmodiumfalciparummalaria AT frankonyambu studyofplateletmediatedclumpingadhesionphenotypesinplasmodiumfalciparummalaria |