Neutrophil Rolling on Patches of Selectin

Abstract

Listen

Translate article

For a neutrophil to reach an infection site, it circulates through the blood, adheres to the blood vessel wall, initially rolling, then adhering firmly; finally, the neutrophil actively passes through the wall. The initial rolling of a neutrophil is primarily mediated by adhesion of receptors on the neutrophil to selectins on the blood vessel wall. A neutrophil has hundreds of surface protrusions called microvilli, little fingers; most of the adhesion receptors involved in initial rolling are situated on the tips of microvilli. Here, I present theoretical analysis showing that the dynamics of a rolling neutrophil are qualitatively different depending on whether its microvilli are typically bound with single or multiple receptors. The role of multiple binding on a single microvillus increases with the surface concentration of selectin, up to a limit. P-selectin is ordinarily stored in granules in an endothelial cell, and released in patches on the cell membrane during inflammation. There is some experimental evidence suggesting additionally that patches of P-selectin are concentrated near the boundaries of endothelial cells. Here, a numerical model of neutrophil rolling which accounts for discrete receptor-ligand interactions is used to show how patchy distribution of P-selectin can promote neutrophil arrest and direct neutrophils to boundaries of endothelial cells, facilitating extravasation.