Fluid Shear Response in Leukocytes

The passage of leukocytes from the bone marrow into the active circulation requires cell migration with all its requirements, such as pseudopod projection by cytoplasmic actin polymerization in coordination with cyclic membrane adhesion and detachment. The cells have to be fully activated. But leukocytes that are collected in venous or arterial blood samples from a healthy individual have few of these indicators for cell activation. They are almost perfectly round cells, exhibit low levels of membrane adhesion, and pass readily through the microcirculation without entrapment in capillaries or adhesion to venular or arteriolar endothelium. In contrast, if an inflammatory stimulus is applied, circulating leukocytes are perfectly capable at any moment to adhere to and migrate on or across the endothelium. This evidence suggests that there exists a mechanism that serves to de-activate circulating leukocytes. Furthermore, in the presence of inflammatory mediators, this mechanism may be abolished and as a result activated leukocytes may appear in the circulation. We hypothesize here that this mechanism is due to mechanical fluid shear. This chapter is focused on the shear response of circulating leukocytes. The chapters by Dr. Frangos and Tarbel address the fluid shear response in endothelial cells and smooth muscle cells.