doi:10.1016/S0166-6851(03)00075-6
Copyright © 2003 Elsevier Science B.V. All rights reserved.
ICAM-1 can play a major role in mediating P. falciparum adhesion to endothelium under flow
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Carolyn Graya, Christopher McCormickb, Gareth Turnerc and Alister Craig
, 
, a
a Molecular Biochemistry and Parasitology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK
b School of Biochemistry and Molecular Biology, University of Leeds, Leeds LS2 9JT, West Yorkshire, UK
c Division of Molecular Histopathology, Addenbrooke’s Hospital, University Department of Pathology, Box 231, Level 3, Cambridge CB2 2QQ, UK
Received 3 January 2003;
revised 25 February 2003;
accepted 2 March 2003. ;
Available online 9 April 2003.
Abstract
We have investigated the importance of adhesion molecule co-operation in mediating Plasmodium falciparum adhesion to endothelial cells under flow conditions. Using three laboratory parasite lines and a patient isolate which differ in their ICAM-1 and CD36-binding avidity, we found that blockade of ICAM-1 and CD36 separately reduced IRBC adhesion by up to 95 and 50%, respectively. These results confirm previous data showing that ICAM-1 and CD36 synergize to mediate adhesion, but differ in demonstrating that without ICAM-1, binding under flow conditions is severely impaired. Thus, in this system, ICAM-1 is critical for P. falciparum adhesion to activated endothelium and once bound, synergy with CD36 mediates the majority (≥98%) of adhesion.
Author Keywords: ICAM-1; CD36; Plasmodium falciparum; Adhesion; HDMEC; HUVEC
Abbreviations: HDMEC, human dermal microvascular endothelial cells; HUVEC, human umbilical vein endothelial cells; ICAM-1, intercellular adhesion molecule-1; IRBC, infected red blood cells; mAb, monoclonal antibody; TNF-α, tissue necrosis factor-α
Fig. 1. ICAM-1-mediated IRBC adhesion under flow conditions. Flow assays (four experiments) were carried out as described in the methods. Briefly, IRBC (3% parasitaemia, 1% haematocrit) were flowed over ICAM-1-coated (25 μg ml−1) microslides at a wall shear stress of 0.05 Pa. (A) The mean number, and standard error of the means, of stationary A4, ItG, JDP8 and C24 IRBC per mm2. (B) Rolling velocity (μm s−1) of individual A4, ItG, JDP8 and C24 IRBC from all experiments.
Fig. 2. IRBC adhesion to HUVEC under flow conditions. Flow assays (four experiments) were carried out as described in the methods. Briefly, confluent microslides were incubated for 1 h with no antibody (no Ab), control antibody (CIg, 4 μg ml−1) or anti-ICAM-1 mAb (αICAM-1, 4 μg ml−1) prior to use. IRBC (3% parasitaemia, 1% haematocrit) were flowed over microslides at a wall shear stress of 0.05 Pa. (A–C) The mean number, and standard error of the means, of stationary A4 (A), ItG (B) and JDP8 (C) IRBC per mm2. (D–F) Rolling velocity (μm s−1) of individual A4 (D), ItG (E) and JDP8 (F) IRBC from all experiments. *: Statistically significant if P<0.05.
Fig. 3. Importance of ICAM-1-mediated IRBC adhesion to HDMEC under flow conditions. Flow assays (four experiments) were carried out as described in the methods. Briefly, confluent microslides were incubated for 1 h with no antibody (no Ab), control antibody (CIg, 4 μg ml−1), anti-ICAM-1 mAb (αICAM-1, 4 μg ml−1) or anti-CD36 mAb (αCD36, 4 μg ml−1) prior to use. IRBC (3% parasitaemia, 1% haematocrit) were flowed over microslides at a wall shear stress of 0.05 Pa. (A–C) The mean number, and standard error of the means, of stationary A4 (A), ItG (B) and JDP8 (C) IRBC per mm2. (D–F) Rolling velocity (μm s−1) of individual A4 (D), ItG (E) and JDP8 (F) IRBC from all experiments. *: Statistically significant if P<0.05.
Table 1. Adhesion of A4, ItG, JDP8 and C24 IRBC per mm2 to purified ICAM-1 and CD36
Static assays were carried out as described in the methods. Briefly, IRBC (3% parasitaemia, 1% haematocrit) were incubated for 1 h with re-suspension every 10 min. Data shown is the mean number of IRBC per mm2 ± S.E. of the means of 3–5 experiments.
Table 2. Adhesion of A4, ItG, JDP8 and C24 IRBC per mm2 to HUVEC and HDMEC
Static assays were carried out as described in the methods. Briefly, IRBC (3% parasitaemia, 1% haematocrit) were incubated for 1 h with re-suspension every 10 min. Data shown is the mean number of IRBC per mm2 ± S.E. of the means of 3–5 experiments.
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