A mechanisms for control of mechanotransduction in leukocytes

Human leukocytes retract pseudopods due to active actin polymerization and return into a spherical state in response to physiological fluid shear stresses (of the order of 1 dyn/cm/sup 2/). Fluid shear stress also serves to detach the leukocytes by a attenuation of the molecular membrane adhesion mechanism. All leukocytes derived from individuals without cardiovascular complications respond to fluid shear stress. In contrast, during inflammatory conditions pseudopod projection and firm adhesion on endothelium can be observed in a subgroup of leukocytes positioned on microvessels with normal blood flow and fluid shear stresses. Thus there exists a mechanisms that serves to regulate the shear stress response. The authors examine here several mechanisms that influence shear stress response of leukocytes and demonstrate that both inflammatory mediators as well as depletion of cGMP serves to attenuate the shear stress response in-vivo and in-vitro. These results indicate that there exist several mechanisms to attenuate mechanotransduction pathways in circulating leukocytes and thereby eliminate the anti-inflammatory action of normal physiological fluid shear stress.