Fluid shear stress-mediated mechanotransduction in circulating leukocytes and its defect in microvascular dysfunction

Leukocytes (neutrophils, monocytes) in the active circulation exhibit multiple phenotypic indicators for a low level of cellular activity, like lack pseudopods and minimal amounts activated, cell-adhesive integrins on their surfaces. In contrast, before these cells enter bone marrow or when they recross endothelium into extravascular tissues peripheral organs are fully activated. We review here multifaceted mechanism mediated by fluid shear stress that can serve to deactivate leukocytes circulation. The controls pseudopod formation via FPR receptor, same receptor responsible projection localized actin polymerization. bioactivity macromolecular factors blood plasma interfere with stimulation flow, such as proteolytic cleavage extracellular domain membrane actions cholesterol, leads defective ability respond depolymerization. cell reaction involves CD18 integrins, nitric oxide, cGMP Rho GTPases, is attenuated presence inflammatory mediators modified glucocorticoids. abolished disease models (genetic hypertension hypercholesterolemia) leading an increased number activated enhanced microvascular resistance entrapment. addition role binding biochemical agonists/antagonists, receptors appear play second role: monitor local levels. control many circulating types lymphocytes, stem cells, tumor remains be elucidated.