Broad inhibition of plasmodium falciparum cytoadherence by -epigallocatechin gallateReport as inadecuate




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Malaria Journal

, 10:348

First Online: 01 December 2011Received: 12 September 2011Accepted: 01 December 2011

Abstract

BackgroundThe surface antigen Pf EMP-1 is a key virulence factor of the human malaria parasite implicated in the cytoadherence of Plasmodium falciparum infected erythrocytes to a range of receptors on host endothelium. Among these host receptors, binding to ICAM-1 is related to cerebral malaria. The majority of the mortality in children with cerebral malaria is seen within 24 h of hospital admission despite the use of effective anti-parasite drugs, therefore, the development of adjunctive therapies is urgently needed.

The polyphenolic compound +-epigallocatechin gallate +-EGCG has been previously evaluated for anti-adhesive properties using a small number of laboratory parasite isolates. Here, this property is further explored using a new panel of ICAM-1-binding patient isolates of P. falciparum to ascertain if +-EGCG might be effective as a broad spectrum inhibitor of ICAM-1-based cytoadherence.

MethodsPlasmodium falciparum lines, including A4 and ItG as positive controls and nine new ICAM-1 binding patient isolates, were allowed to bind with ICAM-1-Fc protein under static assay conditions in the presence and absence of 50 μM +-EGCG. Adhesion levels of all the parasite strains were quantified by microscopy as the mean number of infected erythrocyte IE bound per mm of surface area and statistical comparisons were made to demonstrate the effect of +-EGCG on the binding of various parasite variants to human ICAM-1.

ResultsThis study revealed that binding of patient isolates to ICAM-1 was reduced significantly with inhibition levels of 37% in patient isolate BC-12 up to a maximum of 80% in patient isolate 8146 at 50 μM +-EGCG.

ConclusionEvaluation of the anti-adhesive property of +-EGCG against a new panel of ICAM-1-binding patient isolates of P. falciparum showed that this inhibitor, identified as potential mimic of the L43 loop of human ICAM-1, was effective at blocking cytoadherence.

KeywordsPlasmodium falciparum Malaria Cytoadherence Inhibitor ICAM-1 List of abbreviationsBSABovine Serum Albumen

EGCGEpigallocatechin gallate

ICAM-1Intercellular Adhesion Molecule - 1

IEInfected erythrocyte

PBSPhosphate buffered saline

PfEMP-1Plasmodium falciparum erythrocyte membrane protein - 1

RBCRed blood cell

Electronic supplementary materialThe online version of this article doi:10.1186-1475-2875-10-348 contains supplementary material, which is available to authorized users.

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Author: Pradeep R Patil - Sandra Gemma - Giuseppe Campiani - Alister G Craig

Source: https://link.springer.com/







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