The contribution of adhesion forces to the leukocyte response to shear stress

Leukocyte emigration at inflammatory sites requires rolling along microvessels, firm adhesion, cell spreading and active migration. While these activities require leukocytes to shift from a passive to an active state, the mechanisms underlying these phenomena are incompletely understood. The leukocyte response to fluid shear stress may play a regulatory role. We previously showed that glass-adherent and initially passive leukocytes exposed to a controlled fluid shear stress project pseudopodia, extend lamellipodia and extensively spread in an amplitude and duration dependent manner. The aim of the current investigation was to elucidate mechanisms underlying the transformation of adherent leukocytes from a round to spread configuration by fluid shear stress. Several approaches were used to manipulate membrane adhesive and repulsive forces in human leukocytes before exposure to fluid shear stress of /spl sim/2 dyn/cm/sup 2/. Cell geometric parameters from each of the interventions were compared to control values. Manipulating adhesion forces both enhanced and diminished the cell spreading response to fluid shear stress.