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Amplification of P. falciparum Cytoadherence through Induction of a Pro-Adhesive State in Host Endothelium.

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Wu, Yang, Szestak, Tadge, Stins, Monique and Craig, Alister ORCID: https://orcid.org/0000-0003-0914-6164 (2011) 'Amplification of P. falciparum Cytoadherence through Induction of a Pro-Adhesive State in Host Endothelium.'. PLoS ONE, Vol 6, Issue 10, e24784.

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Abstract

This study examined the ability of P.falciparum-infected erythrocytes (IE) to induce a pro-adhesive environment in the host endothelium during malaria infection, prior to the systemic cytokine activation seen in the later phase of disease. Previous work had shown increases in receptor levels but had not measured to actual impact on IE binding. Using a co-culture system with a range of endothelial cells (EC) and IE with different cytoadherent properties, we have characterised the specific expression of adhesion receptors and subsequent IE binding by FACS and adhesion assays. We have also examined the specific signalling pathways induced during co-culture that are potentially involved in the induction of receptor expression. The results confirmed that ICAM-1 is up-regulated, albeit at much lower levels than seen with TNF activation, in response to co-culture with infected erythrocytes in all three tissue endothelial cell types tested but that up-regulation of VCAM-1 is tissue-dependent. This small increase in the levels of EC receptors correlated with large changes in IE adhesion ability. Co-culture with either RBC or IE increased the potential of subsequent adhesion indicating priming/modulation effects on EC which make them more susceptible to adhesion and thereby the recruitment of IE. Trypsin surface digestion of IE and the use of a Pfsbp1-knockout (ko) parasite line abrogated the up-regulation of ICAM-1 and reduced IE binding to EC suggesting that PfEMP-1 and other molecules exported to the IE surface via the PfSBP1 pathway are major mediators of this phenotype. This was also supported by the higher induction of EC adhesion receptors by adherent IE compared to isogenic, non-adherent lines.

Item Type: Article
Subjects: QX Parasitology > Protozoa > QX 135 Plasmodia
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 695 Parasitic diseases (General)
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 750 Malaria
Faculty: Department: Groups (2002 - 2012) > Molecular & Biochemical Parasitology Group
Digital Object Identifer (DOI): https://doi.org/10.1371/journal.pone.0024784
Depositing User: Mary Creegan
Date Deposited: 11 Nov 2011 16:21
Last Modified: 17 Jul 2019 14:14
URI: https://archive.lstmed.ac.uk/id/eprint/2434

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