Neutrophil motion in straight and tapering P‐selectin‐coated in vitro models of lung capillaries

Abstract

Neutrophil sequestration in lung capillaries is a key step in the inflammatory response to lung infection. Neutrophils were aspirated into capillary‐sized glass microvessels of varying diameters and taper rates coated with soluble P‐selectin or BSA. Cell velocity distributions were measured for pressure differences thought to be present across single pulmonary capillary segments. A creeping motion was observed with velocity significantly lower on P‐selectin than BSA, and that decreased with increasing P‐selectin concentration. The gap width between neutrophil surface and microvessel wall decreased with increasing concentration of P‐selectin while the force exerted by the bonds on the cell increased. It was also shown that high concentrations of anti‐P‐selectin F(ab΄)2 were effective to inhibit the P‐selectin mediated adhesion. These results demonstrate that even low densities of P‐selectin mediate neutrophil adhesion in the pulmonary capillary geometry. No mechanical arrest of neutrophils was observed in tapering vessels with taper angles of up to 9°, however, there is a transition point where cells slow down drastically, that does not depend on the P‐selectin concentrations, taper rate, or aspiration pressure. These results suggest that neutrophil arrest is primarily influenced by adhesion rather than mechanical trapping. This work was supported by grant BES‐0547165 from the NSF.