Control of fluid shear response in circulating leukocytes by integrins

Recent evidence shows that circulating leukocytes respond not only to humoral inflammatory mediators but also to fluid stresses. Application of fluid shear stress (of the order of 1-10 dyn/cm2) to fresh migrating leukocytes leads to initial retraction of pseudopods, an important step to facilitate normal passage of leukocytes through the microcirculation and to prevent spreading on the endothelium. The ability to respond to fluid shear stress, however, may be regulated under different physiological conditions. In the current study, we examine the role of integrins in the fluid shear response as measured by pseudopod retraction with the use of antibodies against human neutrophil beta1 and beta2 integrins. Neutrophils adhering via beta2 integrins exhibit normal ability to project pseudopods and to migrate. Such cells show normal response to fluid shear with rapid pseudopod retraction. In contrast, attachment via beta1 integrins leads to firmly adhesive leukocytes, spreading and almost no cell migration. Such leukocytes exhibit a significantly attenuated ability for pseudopod retraction under fluid shear. These results suggest that integrins may serve as a regulating mechanism for fluid shear response in human leukocytes. Attachment via beta1 integrins may lead to an abolishment of the fluid shear response.