P-Selectin and ICAM-1 synergy in mediating THP-1 monocyte adhesion in hemodynamic flow is length dependent

Abstract

The tightly orchestrated recruitment of monocytes, whose progeny are critical to the progression and resolution of various physiological and pathophysiological processes, is implicated in the time course, severity, and resolution of pathology. Using a microfluidic-based cell adhesion assay integrating spatiotemporal analyses and micropatterning of adhesive proteins, we interrogated the effects of adhesive molecule presentation length, which varies in vivo with disease and stage, on THP-1 monocyte cell rolling versus firm adhesion mediated by P-selectin and/or ICAM-1 in hemodynamic flow. Our results indicate that co-presentation of P-selectin and ICAM-1 substantially decreases the length of adhesive substrate required to sustain adhesion in flow and that P-selectin functions synergistically with ICAM-1 to substantially enhance THP-1 firm adhesion. This synergy was found to furthermore correlate with diminished cell rolling velocities and length-enhanced secondary cell capture. Our results suggest pathophysiological ramifications for local remodeling of the inflamed microvascular microenvironment in directing the efficiency of monocyte trafficking.