The Effect of Anti-Rosetting Agents against Malaria Parasites under Physiological Flow Conditions
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The Effect of Anti-Rosetting Agents against Malaria Parasites under Physiological Flow Conditions. / Adams, Yvonne; Rowe, J. Alexandra.
In: PLoS ONE, Vol. 8, No. 9, e73999, 16.09.2013.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - The Effect of Anti-Rosetting Agents against Malaria Parasites under Physiological Flow Conditions
AU - Adams, Yvonne
AU - Rowe, J. Alexandra
PY - 2013/9/16
Y1 - 2013/9/16
N2 - Rosetting remains the dominant malaria parasite adhesion phenotype associated with severe disease and pathogenicity in Africa. The formation of rosettes, whereby a Plasmodium falciparum infected erythrocyte (IE) adheres to two or more non-IEs, is thought to facilitate the occlusion of microvascular blood vessels by adhering to host endothelial cells and other bound IEs. Current methods of determining the rosette-disrupting capabilities of antibodies/drugs have focused on static assays. As IEs in vivo are exposed to shear stresses within the microvasculature, the effect of flow conditions on rosetting requires further examination. This study establishes a new rosetting flow assay using a closed perfusion system together with inverted fluorescence microscopy and image analysis, and confirms previous reports that rosettes exist under shear stresses equivalent to those present in the microvasculature (0.5-1.0 dyn/cm2). Furthermore, we tested the effectiveness of rosette-disrupting PfEMP1 antibodies, heparin and fucoidan over a range of concentrations on two P. falciparum strains, and found no statistically significant differences between the results of static and flow assays. The new flow assay is a valuable addition to the tools available to study rosetting. However, the static assay has good predictive value and remains useful as the standard screening test for rosette-disrupting interventions.
AB - Rosetting remains the dominant malaria parasite adhesion phenotype associated with severe disease and pathogenicity in Africa. The formation of rosettes, whereby a Plasmodium falciparum infected erythrocyte (IE) adheres to two or more non-IEs, is thought to facilitate the occlusion of microvascular blood vessels by adhering to host endothelial cells and other bound IEs. Current methods of determining the rosette-disrupting capabilities of antibodies/drugs have focused on static assays. As IEs in vivo are exposed to shear stresses within the microvasculature, the effect of flow conditions on rosetting requires further examination. This study establishes a new rosetting flow assay using a closed perfusion system together with inverted fluorescence microscopy and image analysis, and confirms previous reports that rosettes exist under shear stresses equivalent to those present in the microvasculature (0.5-1.0 dyn/cm2). Furthermore, we tested the effectiveness of rosette-disrupting PfEMP1 antibodies, heparin and fucoidan over a range of concentrations on two P. falciparum strains, and found no statistically significant differences between the results of static and flow assays. The new flow assay is a valuable addition to the tools available to study rosetting. However, the static assay has good predictive value and remains useful as the standard screening test for rosette-disrupting interventions.
UR - http://www.scopus.com/inward/record.url?scp=84884198034&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0073999
DO - 10.1371/journal.pone.0073999
M3 - Journal article
C2 - 24066091
AN - SCOPUS:84884198034
VL - 8
JO - PLoS ONE
JF - PLoS ONE
SN - 1932-6203
IS - 9
M1 - e73999
ER -
ID: 340559509