title: Molecular mechanisms of cytoadherence in malaria.
abstract: Microbial pathogens subvert host adhesion molecules to disseminate or to enter host cells to promote their own survival. One such subversion is the cytoadherence of Plasmodium falciparum-infected erythrocytes (IRBC) to vascular endothelium, which protects the parasite from being removed by the spleen. The process results in microcirculatory obstruction and subsequent hypoxia, metabolic disturbances, and multiorgan failure, which are detrimental to the host. Understanding the molecular events involved in these adhesive interactions is therefore critical both in terms of pathogenesis and implications for therapeutic intervention. Under physiological flow conditions, cytoadherence occurs in a stepwise fashion through parasite ligands expressed on the surface of IRBC and the endothelial receptors CD36, intercellular adhesion molecule-1 (ICAM-1), P-selectin, and vascular adhesion molecule-1. Moreover, rolling on ICAM-1 and P-selectin increases subsequent adhesion to CD36, indicating that receptors can act synergistically. Cytoadherence may activate intracellular signaling pathways in both endothelial cells and IRBC, leading to gene expression of mediators such as cytokines, which could modify the outcome of the infection.
authors.affiliation: Department of Microbiology and Infectious Diseases and Immunology Research Group, University of Calgary, Calgary, Alberta, Canada T2N 4N1. mho@acs.ucalgary.ca
authors.forename: M
authors.initials: M
authors.lastname: Ho
authors.forename: N J
authors.initials: NJ
authors.lastname: White
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology; D006790:Host-Parasite Interactions / Q000502:physiology*; D006801:Humans; D016778:Malaria, Falciparum / Q000378:metabolism / Q000469:parasitology / Q000503:physiopathology*; D010963:Plasmodium falciparum / Q000502:physiology
chemical_list: D015815:Cell Adhesion Molecules