Mechanotransduction in Cells of the Circulation

Leukocytes in the circulation respond to a wide range of biochemical mediators. Recently we showed that leukocytes also respond to fluid mechanical stresses. They respond in a number of ways: by retraction of pseudopods and by reduction of the membrane adhesion molecules. The fluid shear response is an important mechanism that serves to minimize leukocyte pseudopod formation in the circulation. Reduction of the fluid shear stress in-vivo leads to pseudopod projection and cell spreading. The fluid shear response controls the transendothelial migration of leukocytes into the tissue. The fluid shear response is a powerful control mechanism for the immune system. Centrifugation of leukocytes unfortunately destroys the fluid shear response. Cells without an intact fluid shear response lack the ability to pass through the microcirculation and may become trapped in capillaries.

Our research program is designed to examine the mechanisms for the fluid shear response in leukocytes and microvascular endothelial cells.


Cell Activation in the Microcirculation

Human neutrophils before (top) and after (bottom) activation

Capillary endothelial cells before (left)
and after (right) activation



LeukocyteFluid Shear Response
In Vitro
In Vivo
Occlusion for 15 seconds
Occlusion for 120 seconds
Reperfusion


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