Plasmodium falciparum icam-1-based cytoadherence-related signalling in endothelical cells

Jenkins, Neil; Wu, Yang; Chakravorty, Srabasti; Kai, Oscar; Marsh, Kevin; Craig, Alister

Abstract

Background: Cytoadherence of Plasmodium falciparum infected erythrocytes to host endothelium has been associated with pathology in severe malaria, but despite extensive information on the primary processes involved in the adhesive interactions the mechanisms underlying disease are poorly understood. There is evidence that during cerebral malaria there is subtle, focal alteration in the integrity of the blood-brain barrier. Rather than being passive bystanders, we have considered how endothelial cells might respond to parasite binding with direct effects on barrier function.

Methods: We used an in vitro model of vascular endothelial cells (ECs) and parasite lines varying in their binding properties and compared their ability to stimulate signalling activity. Techniques based on immunoprecipitation were used to detect activity of MAP kinases and Rho GTPase.

Results: We found coculture of parasites with endothelial cells resulted in activation of intracellular signalling proteins. The degree of activation appeared dependent on binding. In human umbilical vein endothelial cells (HUVEC), which rely on adhesion to intercellular adhesion molecule-1 (ICAM-1) for binding, signalling is related to the avidity of the parasite line for ICAM-1, and can be blocked either through the use of anti-ICAM-1 monoclonal antibodies or HUVEC cells with altered ICAM-1 binding properties, namely ICAM-1Kilifi. Human dermal microvascular endothelial cells (HDMEC), which can bind infected erythrocytes via ICAM-1 and CD36, have a more complex pattern of signalling behaviour but this is also dependent on adhesive interactions rather than merely contact between cells.

Conclusions: Signalling via apposition of P.falciparum-infected erythrocytes with host endothelium is dependent, at least in part, on the binding characteristics of the parasite and the host receptors. An understanding of the post-adhesive processes produced by cytoadherence may help us to understand the variable pathology seen in malaria disease and might suggest new therapeutic strategies.

Citation

Jenkins, N., Wu, Y., Chakravorty, S., Kai, O., Marsh, K., & Craig, A. (2008). Plasmodium falciparum icam-1-based cytoadherence-related signalling in endothelical cells. Journal of Infection, 56(4), 299. https://doi.org/10.1016/j.jinf.2008.01.018

• Journal Article Type: Article
• Online Publication Date: Apr 3, 2008
• Publication Date: 2008-04
• Deposit Date: May 14, 2024
• Journal: Journal of Infection
• Print ISSN: 0163-4453
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 56
• Issue: 4
• Pages: 299
• DOI: https://doi.org/10.1016/j.jinf.2008.01.018
• Public URL: https://keele-repository.worktribe.com/output/827359