Michael B Kim1, Ingrid H Sarelius. 1. Department of Biomedical Engineering, University of Rochester, Rochester, NY 14642, USA.
Abstract
OBJECTIVE: To determine the influence of wall shear rate and leukocyte delivery on leukocyte margination, rolling, and adhesion in post-capillary venules. METHODS: Leukocyte-endothelial cell interactions were characterized in cremaster muscle venules of anesthetized mice with video microscopy under control conditions and after 3 h exposure to TNF-alpha. Hemodynamic parameters were measured with fluorescent particle tracking using confocal microscopy. RESULTS: Leukocyte recruitment to the vessel wall and leukocyte rolling increased as a function of wall shear rate (P < 0.05) over the range observed (0-200 s(-1)) in intact post capillary venules. Leukocyte delivery affected recruitment and rolling flux only in activated vessels (P < 0.05). In addition, leukocyte firm adhesion was independent of both wall shear rate and leukocyte delivery, but showed an overall increase in TNF-alpha stimulated tissues (0.9 +/- 0.2 vs. 2.7 +/- 0.6 cells/50 microm). CONCLUSIONS: Leukocytes are delivered to venules in excess of the capacity of the local endothelium to support interactions. Elevated shear forces increase leukocyte recruitment to the vessel wall, which correlates to elevated rolling flux. In contrast, leukocyte firm adhesion is primarily affected by the activation state of the tissue and not by hemodynamic factors. Overall, the capacity of endothelial cells to support leukocyte interactions primarily regulates leukocyte recruitment and is not limited by leukocyte supply.
OBJECTIVE: To determine the influence of wall shear rate and leukocyte delivery on leukocyte margination, rolling, and adhesion in post-capillary venules. METHODS: Leukocyte-endothelial cell interactions were characterized in cremaster muscle venules of anesthetized mice with video microscopy under control conditions and after 3 h exposure to TNF-alpha. Hemodynamic parameters were measured with fluorescent particle tracking using confocal microscopy. RESULTS: Leukocyte recruitment to the vessel wall and leukocyte rolling increased as a function of wall shear rate (P < 0.05) over the range observed (0-200 s(-1)) in intact post capillary venules. Leukocyte delivery affected recruitment and rolling flux only in activated vessels (P < 0.05). In addition, leukocyte firm adhesion was independent of both wall shear rate and leukocyte delivery, but showed an overall increase in TNF-alpha stimulated tissues (0.9 +/- 0.2 vs. 2.7 +/- 0.6 cells/50 microm). CONCLUSIONS: Leukocytes are delivered to venules in excess of the capacity of the local endothelium to support interactions. Elevated shear forces increase leukocyte recruitment to the vessel wall, which correlates to elevated rolling flux. In contrast, leukocyte firm adhesion is primarily affected by the activation state of the tissue and not by hemodynamic factors. Overall, the capacity of endothelial cells to support leukocyte interactions primarily regulates leukocyte recruitment and is not limited by leukocyte supply.
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