Leukocyte adhesion in capillary-sized, P-selectin-coated micropipettes.

OBJECTIVE Leukocyte retention in lung capillaries is observed in normal physiology and following a bacterial infection. It has been hypothesized that cells either become mechanically trapped or adhere to capillary endothelial cells via adhesion molecules. We propose that retention involves both mechanical and adhesive forces and that the biochemical adhesive force is modulated by mechanical forces that alter the area of contact between leukocytes and endothelium. METHODS To probe this hypothesis, an adhesion assay has been developed in which individual HL-60 cells were aspirated into micropipettes pre-coated with P-selectin. Following aspiration, cells were exposed to physiological pressure differences. RESULTS Little adhesion was seen in micropipettes coated with BSA, whereas significant adhesion was observed in micropipettes coated with P-selectin. The frequency of cell arrest on P-selectin in the micropipette was much greater than on P-selectin in a parallel plate flow chamber even though the disruptive force in the micropipette assay exceeds that in the parallel plate flow chamber. These results demonstrate that receptor-ligand interactions can enhance adhesion in a capillary geometry and that differences in capillary geometry vs. venule geometry can significantly influence the adhesive phenotype. CONCLUSIONS Taken together, these observations support the hypothesis that an interplay between mechanical and biochemical adhesive forces can play a major role in retention.