Fibrinogen binding to intercellular adhesion molecule 1: implications for Plasmodium falciparum adhesion

Abstract

Intercellular adhesion molecule 1 (ICAM-1) is an endothelial cell adhesion molecule implicated in cerebral malaria. We investigated whether fibrinogen affects Plasmodium falciparum binding to ICAM-1, as the ICAM-1 binding sites of P. falciparum and fibrinogen overlap. We show that fibrinogen dramatically reduces P. falciparum adhesion to ICAM-1 under flow conditions.

FIG. 1.

Fg inhibits A4 and ItG binding to ICAM-1. Experimental details are as described in the text. Briefly, ICAM-1-coated (10 μg/ml) microslides were incubated with varying concentrations of Fg or fibronectin diluted in binding buffer for 1 h at 37°C. A4 and ItG IRBC (3% parasitemia, 1% hematocrit) were then allowed to flow over the microslides at a wall shear stress of 0.05 Pa. (A and C) The means and standard errors of the means of stationary A4 (A) and ItG (C) IRBC per square millimeter from six different fields in three separate experiments using ICAM-1-coated microslides incubated with either Fg (filled bars) or fibronectin (open bars). (B and D) Rolling velocity (micrometers per second) of individual A4 (B) and ItG (D) IRBC from all three Fg experiments. ∗, statistically significant at P < 0.05.