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Infection and Immunity, June 2005, p. 3271-3277, Vol. 73, No. 6
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.6.3271-3277.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Direct Activation of Human Endothelial Cells by Plasmodium falciparum-Infected Erythrocytes

Nicola K. Viebig,1,2 Ulrich Wulbrand,3 Reinhold Förster,3 Katherine T. Andrews,1,4 Michael Lanzer,1 and Percy A. Knolle2,5*

Hygiene Institut, Abteilung Parasitologie, Universität Heidelberg, Heidelberg, Germany,1 Zentrum für Molekulare Biologie Heidelberg (ZMBH), Universität Heidelberg, Heidelberg, Germany,2 Institut für Immunologie, Medizinische Hochschule Hannover, Hannover, Germany,3 Queensland Institute of Medical Research, Royal Brisbane Hospital, Herston, Brisbane, Australia,4 Institut für Molekulare Medizin und Experimentelle Immunologie, Universität Bonn, Bonn, Germany5

Received 5 August 2004/ Returned for modification 7 September 2004/ Accepted 23 January 2005

Cytoadherence of Plasmodium falciparum-infected erythrocytes (PRBC) to endothelial cells causes severe clinical disease, presumably as a of result perfusion failure and tissue hypoxia. Cytoadherence to endothelial cells is increased by endothelial cell activation, which is believed to occur in a paracrine fashion by mediators such as tumor necrosis factor alpha (TNF-{alpha}) released from macrophages that initially recognize PRBC. Here we provide evidence that PRBC directly stimulate human endothelial cells in the absence of macrophages, leading to increased expression of adhesion-promoting molecules, such as intercellular adhesion molecule 1. Endothelial cell stimulation by PRBC required direct physical contact for a short time (30 to 60 min) and was correlated with parasitemia. Gene expression profiling of endothelial cells stimulated by PRBC revealed increased expression levels of chemokine and adhesion molecule genes. PRBC-stimulated endothelial cells especially showed increased expression of molecules involved in parasite adhesion but failed to express molecules promoting leukocyte adhesion, such as E-selectin and vascular cell adhesion molecule 1, even after challenge with TNF-{alpha}. Collectively, our data suggest that stimulation of endothelial cells by PRBC may have two effects: prevention of parasite clearance through increased cytoadherence and attenuation of leukocyte binding to endothelial cells, thereby preventing deleterious immune reactivity.

* Corresponding author. Mailing address: Institut für Molekulare Medizin und Experimentelle Immunologie, Friedrich-Wilhelms-Universität Bonn, Sigmund-Freud-Str. 25, 53105 Bonn, Germany. Phone: 49 228 287 1050. Fax: 49 228 287 1052. E-mail: percy.knolle{at}ukb.uni-bonn.de.

Editor: J. L. Flynn

Infection and Immunity, June 2005, p. 3271-3277, Vol. 73, No. 6
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.6.3271-3277.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Tripathi, A. K., Sullivan, D. J., Stins, M. F. (2006). Plasmodium falciparum-Infected Erythrocytes Increase Intercellular Adhesion Molecule 1 Expression on Brain Endothelium through NF-{kappa}B.. Infect. Immun. 74: 3262-3270 [Abstract] [Full Text]  


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