TNF-a-Activated Endothelium: Augmentation by Erythrocytes

The adhesive and hemodynamic forces that lead to lymphocyte rolling and arrest on activated endothelium and the biophysical role of various adhesion molecules and blood elements in this process are poorly understood. By quantifying their behavior both in vivo and in vitro, we show here that erythrocytes facilitate selectinand integrin-mediated rolling and binding of T-lymphocytes on tumor necrosis factor a-activated endothelium. The relative contribution of selectins and integrins to this process can be distinguished by using a simple mathematical expression of lymphocyte capture within the range of physiological shear stress. The need for selectin participation in lymphocyte capture increases with shear stress (>1 dyn/cm2), and both ,B1 and ,B2 integrins act in synergy to produce adhesive drag on captured cells. These findings are potentially useful in developing strategies for intervening with T-cells in a variety of normal and pathological responses as well as for the delivery of genetically modified T-cells to their targets in vivo.

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