The identification of a subgroup of leukocytes that do not respond to fluid shear stress by pseudopod retraction

A necessary step in leukocyte activation and migration out of the microcirculation is pseudopod formation. It has previously been shown (F. Moazzam et al., 1997) that fluid shear stresses on the order of those found in the microcirculation (1-10 dyn/cm/sup 2/) cause activated leukocytes to retract their pseudopods and cease to migrate. In-vitro, application of inflammatory stimulators to neutrophils on glass slides causes a dose dependent percentage of the cells to enter one of two states, the first of which is a highly spread out morphology in which the cells are insensitive to fluid shear stress (S. Fukuda et al.). The second is the more typical pseudopod forming morphology of activated neutrophils, in which the cells continue to respond to fluid shear stress by retracting pseudopods. The cells in the shear stress non-responsive group are much less likely to migrate in response to a chemotactic gradient than a shear stress responsive neutrophil. Furthermore, their numbers are effected by both the level of intracellular cGMP and the coating of the substrate with fibronectin, suggesting a connection between this intercellular mediator and integrin adhesion in controlling the neutrophil response to fluid shear stress.