The online version of this article (doi:10.1186/1475-2875-11-33) contains supplementary material, which is available to authorized users.
The authors declare that they have no competing interests.
The study was conceived by JCS and designed by JCS, AGC, SK and BS. The assays were performed by FAF with field support from AS, MAH and LCW. The manuscript was prepared by JCS, ACG, and SK. All authors had the opportunity to read and approve the manuscript.
Cytoadherence of infected red blood cells to brain endothelium is causally implicated in malarial coma, one of the severe manifestations of falciparum malaria. Cytoadherence is mediated by specific binding of variant parasite antigens, expressed on the surface of infected erythrocytes, to endothelial receptors including, ICAM-1, VCAM and CD36. In fatal cases of severe falciparum malaria with coma, blood vessels in the brain are characteristically congested with infected erythrocytes. Brain sections from a fatal case of knowlesi malaria, but without coma, were similarly congested with infected erythrocytes. The objective of this study was to determine the binding phenotype of Plasmodium knowlesi infected human erythrocytes to recombinant human ICAM-1, VCAM and CD36.
Five patients with PCR-confirmed P. knowlesi malaria were recruited into the study with consent between April and August 2010. Pre-treatment venous blood was washed and cultured ex vivo to increase the proportion of schizont-infected erythrocytes. Cultured blood was seeded into Petri dishes with triplicate areas coated with ICAM-1, VCAM and CD36. Following incubation at 37°C for one hour the dishes were washed and the number of infected erythrocytes bound/mm2 to PBS control areas and to recombinant human ICAM-1 VCAM and CD36 coated areas were recorded. Each assay was performed in duplicate. Assay performance was monitored with the Plasmodium falciparum clone HB3.
Blood samples were cultured ex vivo for up to 14.5 h (mean 11.3 ± 1.9 h) to increase the relative proportion of mature trophozoite and schizont-infected red blood cells to at least 50% (mean 65.8 ± 17.51%). Three (60%) isolates bound significantly to ICAM-1 and VCAM, one (20%) isolate bound to VCAM and none of the five bound significantly to CD36.
Plasmodium knowlesi infected erythrocytes from human subjects bind in a specific but variable manner to the inducible endothelial receptors ICAM-1 and VCAM. Binding to the constitutively-expressed endothelial receptor CD36 was not detected. Further work will be required to define the pathological consequences of these interactions.
Aikawa M, Iseki M, Barnwell JW, Taylor D, Oo MM, Howard RJ: The pathology of human cerebral malaria. Am J Trop Med Hyg. 1990, 43: 30-37. PubMed
Su XZ, Heatwole VM, Wertheimer SP, Guinet F, Herrfeldt JA, Peterson DS, Ravetch JA, Wellems TE: The large diverse gene family var encodes proteins involved in cytoadherence and antigenic variation of Plasmodium falciparu-infected erythrocytes. Cell. 1995, 82: 89-100. 10.1016/0092-8674(95)90055-1. CrossRefPubMed
Turner GD, Morrison H, Jones M, Davis TME, Looareesuwan S, Buley ID, Gatter KC, Newbold CI, Pukritayakamee S, Nagachinta B, White NJ, Berendt AR: An immunohistochemical study of the pathology of fatal malaria. Evidence for widespread endothelial activation and a potential role for intercellular adhesion molecule-1 in cerebral sequestration. Am J Pathol. 1994, 145: 1057-1069. PubMedCentralPubMed
Udomsangpetch R, Taylor BJ, Looareesuwan S, White NJ, Elliott JF, Ho M: Receptor specificity of clinical Plasmodium falciparu isolates: nonadherence to cell-bound E-selectin and vascular cell adhesion molecule-1. Blood. 1996, 88: 2754-2760. PubMed
McCormick CJ, Craig A, Roberts D, Newbold CI, Berendt AR: Intercellular adhesion molecule-1 and CD36 synergize to mediate adherence of Plasmodium falciparu-infected erythrocytes to cultured human microvascular endothelial cells. J Clin Invest. 1997, 100: 2521-2529. 10.1172/JCI119794. PubMedCentralCrossRefPubMed
Udomsangpetch R, Reinhardt PH, Schollaardt T, Elliott JF, Kubes P, Ho M: Promiscuity of clinical Plasmodium falciparu isolates for multiple adhesion molecules under flow conditions. J Immunol. 1997, 158: 4358-4364. PubMed
Ochola LB, Siddondo BR, Ocholla H, Nkya S, Kimani EN, Williams TN, Makale JO, Liljander A, Urban BC, Bull PC, Szestak T, Marsh K, Craig AG: Specific receptor usage in Plasmodium falciparu cytoadherence is associated with disease outcome. PLoS One. 2011, 6: e14741-10.1371/journal.pone.0014741. PubMedCentralCrossRefPubMed
Turner GD, Ly VC, Nguyen TH, Tran TH, Nguyen HP, Bethell D, Wyllie S, Louwrier K, Fox SB, Gatter KC, Day NP, Tran TH, White NJ, Berendt AR: Systemic endothelial activation occurs in both mild and severe malaria. Correlating dermal microvascular endothelial cell phenotype and soluble cell adhesion molecules with disease severity. Am J Pathol. 1998, 152: 1477-1487. PubMedCentralPubMed
Newbold C, Warn P, Black G, Berendt A, Craig A, Snow B, Msobo M, Peshu N, Marsh K: Receptor-specific adhesion and clinical disease in Plasmodium falciparu. Am J Trop Med Hyg. 1997, 57: 389-398. PubMed
- Cytoadherence and virulence - the case of Plasmodium knowlesi malaria
Farrah A Fatih
Lu Chan Woon
Alister G Craig
- BioMed Central
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