Neutrophil adhesion to P‐selectin/ICAM‐1 in an in vitro model of a lung capillary

Abstract

Neutrophil arrest in alveolar capillaries is a necessary part of the response to infection in the lung. It has been hypothesized that neutrophils either become mechanically trapped or adhere to capillary endothelial cells via adhesion molecules. We propose that arrest involves both mechanical and adhesive forces and that the adhesive force is modulated by mechanical forces that alter the contact area. Micropipettes (tip ID = 5.5–8.5 μm) pre-coated with P-selectin or ICAM-1 were used to model lung capillaries. Following aspiration, individual neutrophils were exposed to physiological pressure differences and the cell motion and arrest were tracked during video microscopy. Significantly more adhesion was seen in micropipettes coated with P-selectin or ICAM-1 than in micropipettes coated with BSA. Neutrophils arrest firmly in the micropipette on concentrations of P-selectin that lead to rolling or no adhesion in a parallel plate flow chamber. The results suggest that the large contact area imposed on the aspirated cell by the capillary geometry leads to a more durable adhesion under higher disrupting forces than that seen for cells in venules. This also implies that lower density of P-selectin can mediate arrest in capillaries than in venules. This work was supported by an award from the American Heart Association (DFJT), CAREER grant BES-0547165 from NSF (DFJT) and grant GM057640 from NIH (DJG).