Rheological analysis of the adhesive interactions of red blood cells parasitized by Plasmodium falciparum

Abstract

Adhesion of parasitized red blood cells (RBCs) to vascular endothelium is thought to be a key factor in the pathology of falciparum malaria. However, quantitative analyses of the intercellular forces and of the effects of flow on adhesion have been lacking. We have characterized cytoadhesion of RBCs parasitized by the strains ITO4 (which can bind to receptors ICAM-1 or CD36) and FCR3A2 (which can bind to CD36 only) using micropipette manipulation and flow chamber techniques. Target cells were unfixed or glutaraldehyde-fixed human umbilical vein endothelial cells (HUVEC, bearing ICAM-1 only) or human amelanotic melanoma cells (C32, bearing CD36 and ICAM-1). In the static, micropipette assay, 60% to 70% of parasitized cells would adhere when tested at up to three successive sites. The percentage of cells adhering and the force required for their detachment (approximately 10(- 10) N) were similar for each combination of parasite strain and adhesion target (ITO4/HUVEC, ITO4/C32, FCR3A2/C32). In the flow chamber, efficiency of initial adhesion of parasitized cells was essentially constant (at about 1%) up to a stress of 0.1 Pa, and then decreased rapidly with increasing stress. Either receptor (ICAM-1 or CD36) could immobilize flowing cells at a physiologic flow stress (0.1 Pa), but the numbers of cells adhering varied for the different combinations (ITO4/C32 greater than ITO4/HUVEC greater than FCR3A2/C32). When flow was increased in steps, adhered cells were gradually washed off but many could withstand stresses at which they would not initially adhere. The force for detachment estimated in this way was similar to the pipette value, and again, was similar for the different combinations of strains and targets. Adhesion from flow depends on the affinity between surfaces being above a critical level, and once adhesion is established, the fracture energy determines resistance to disruption of adhesion. The results show that the fracture energy is greater than the affinity (ie, that adhesion becomes stabilized after it is initially established) and that the ratio of affinity to fracture energy is different for different receptor/ligand pairs, with ICAM-1 appearing to be the more efficient immobilizing receptor. Also, static and flow-based assays of adhesion clearly differ; the affinity is less critical in the static situation, so that most parasitized cells were capable of adhering in a static assay, but fewer did so under flow. Adhesiveness varied markedly from cell to cell, both for targets and parasitized cells.(ABSTRACT TRUNCATED AT 400 WORDS).

Expression dynamics and physiologically relevant functional study of STEVOR in asexual stages ofPlasmodium falciparuminfection

“…This value is comparable to the rosette binding strength of 440 ± 130 pN, as observed in one of the earlier studies (Nash et al, 1992b). In another study, average detachment forces of~100 pN were observed between iRBC and cultured endothelial cells lines expressing CD36 and ICAM-1 (Nash et al, 1992a). A more recent study quantifies the average adhesive forces between FCR3CSA late-stage iRBC and CSA-expressing CHO cells to be in the range of 100-200 pN (unpublished data).…”

New insights into the altered adhesive and mechanical properties of red blood cells parasitized by Babesia bovis

“…Interestingly, PRBCs infected with the virulent parasite line could still adhere to both targets at stresses at which the avirulent line could not (0.4 Pa and greater). For Anderson parasites, the efficiency of adhesion (defined as the percentage of PRBCs that adhered during their passage through the flow chamber) at 0.1 Pa was approximately 1.5% and is similar to the efficiency previously measured for human RBC infected with P. falciparum (Nash et al, 1992). Once PRBCs had adhered, the interaction was strong ( Fig.…”

Inflammatory mediators promote strong sickle cell adherence to endothelium under venular flow conditions

“…Adherence must be rapid enough to occur while the red cell is in the microcirculation, extensive enough to interrupt tissue perfusion, and strong enough to oppose reperfusion pressures (or shear forces) that will dislodge occlusive plugs. To better understand how flow and receptor-ligand pathways may regulate sickle cell adherence, a biophysical detachment assay [28][29][30] was utilized to study the quantity and strength of sickle erythrocyte adherence to endothelium as a function of flow conditions and adherence pathways. Ultimately, understanding the kinetics, strength, and level of adherence and detachment is important in defining the role of sickle erythrocyte adherence in initiating and propagating vasoocclusive complications.…”