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Stephen A Douglas - One of the best experts on this subject based on the ideXlab platform.
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role of p38 map kinase in postcapillary venule Leukocyte adhesion induced by ischemia reperfusion injury
Pharmacological Research, 2005Co-Authors: Douglas G Johns, Zhaohui Ao, Robert N Willette, Colin H Macphee, Stephen A DouglasAbstract:Abstract Inflammation and Leukocyte activation/infiltration play a major role in the initiation and progression of cardiovascular diseases including atherosclerosis and heart failure. Acute p38 mitogen-activated protein kinase (MAPK) pathway inhibition attenuates tissue damage and Leukocyte accumulation in myocardial ischemia/reperfusion injury, although its effect on the acute phase of Leukocyte recruitment has not been elucidated. The purpose of this study was to test the hypothesis that acute treatment of rats with a selective p38 inhibitor, SB-239063, inhibits ischemia/reperfusion-induced Leukocyte-endothelial adhesion in vivo. Male Sprague–Dawley rats were treated with either SB-239063 (10 mg kg−1), dexamethasone (3 mg kg−1) or vehicle 1 h prior to ischemia. Postcapillary venules were observed microscopically in exteriorized, superfused cremaster tissue. Leukocytes were fluorescently labeled in vivo using intravenous rhodamine 6G. Leukocyte adhesion, rolling, and rolling velocities were quantitated prior to 30 min ischemia, and at several time points during a 90 min reperfusion period. Ischemia caused a 3-fold increase in adherent Leukocytes 5 min following reperfusion, a response that was maintained throughout the monitoring period (90 min) in vehicle-treated animals. SB-239063, at a dose known to inhibit p38 MAPK activity in vivo (10 mg kg−1), had no effect on ischemia/reperfusion-induced Leukocyte adhesion, the number of rolling Leukocytes, rolling velocities during the reperfusion period or adhesion molecule expression (P-, E-selectin, VCAM-1, ICAM-1). In contrast, dexamethasone completely blocked Leukocyte adhesion in response to ischemia/reperfusion, and reduced expression of E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). We conclude that p38 MAPK may not play a role in initial Leukocyte recruitment in response to ischemia/reperfusion injury, but could affect Leukocyte emigration, thereby resulting in increased Leukocyte accumulation in ischemic-reperfused tissue.
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Role of p38 MAP kinase in postcapillary venule Leukocyte adhesion induced by ischemia/reperfusion injury.
Pharmacological Research, 2005Co-Authors: Douglas G Johns, Zhaohui Ao, Robert N Willette, Colin H Macphee, Stephen A DouglasAbstract:Abstract Inflammation and Leukocyte activation/infiltration play a major role in the initiation and progression of cardiovascular diseases including atherosclerosis and heart failure. Acute p38 mitogen-activated protein kinase (MAPK) pathway inhibition attenuates tissue damage and Leukocyte accumulation in myocardial ischemia/reperfusion injury, although its effect on the acute phase of Leukocyte recruitment has not been elucidated. The purpose of this study was to test the hypothesis that acute treatment of rats with a selective p38 inhibitor, SB-239063, inhibits ischemia/reperfusion-induced Leukocyte-endothelial adhesion in vivo. Male Sprague–Dawley rats were treated with either SB-239063 (10 mg kg−1), dexamethasone (3 mg kg−1) or vehicle 1 h prior to ischemia. Postcapillary venules were observed microscopically in exteriorized, superfused cremaster tissue. Leukocytes were fluorescently labeled in vivo using intravenous rhodamine 6G. Leukocyte adhesion, rolling, and rolling velocities were quantitated prior to 30 min ischemia, and at several time points during a 90 min reperfusion period. Ischemia caused a 3-fold increase in adherent Leukocytes 5 min following reperfusion, a response that was maintained throughout the monitoring period (90 min) in vehicle-treated animals. SB-239063, at a dose known to inhibit p38 MAPK activity in vivo (10 mg kg−1), had no effect on ischemia/reperfusion-induced Leukocyte adhesion, the number of rolling Leukocytes, rolling velocities during the reperfusion period or adhesion molecule expression (P-, E-selectin, VCAM-1, ICAM-1). In contrast, dexamethasone completely blocked Leukocyte adhesion in response to ischemia/reperfusion, and reduced expression of E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). We conclude that p38 MAPK may not play a role in initial Leukocyte recruitment in response to ischemia/reperfusion injury, but could affect Leukocyte emigration, thereby resulting in increased Leukocyte accumulation in ischemic-reperfused tissue.
Mark W Itensky - One of the best experts on this subject based on the ideXlab platform.
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biomimetic autoseparation of Leukocytes from whole blood in a microfluidic device
Analytical Chemistry, 2005Co-Authors: Sergey S Shevkoplyas, Tatsuro Yoshida, Mark W ItenskyAbstract:Leukocytes comprise less than 1% of all blood cells. Enrichment of their number, starting from a sample of whole blood, is the required first step of many clinical and basic research assays. We created a microfluidic device that takes advantage of the intrinsic features of blood flow in the microcirculation, such as plasma skimming and Leukocyte margination, to separate Leukocytes directly from whole blood. It consists of a simple network of rectangular microchannels designed to enhance lateral migration of Leukocytes and their subsequent extraction from the erythrocyte-depleted region near the sidewalls. A single pass through the device produces a 34-fold enrichment of the Leukocyte-to-erythrocyte ratio. It operates on microliter samples of whole blood, provides positive, continuous flow selection of Leukocytes, and requires neither preliminary labeling of cells nor input of energy (except for a small pressure gradient to support the flow of blood). This effortless, efficient, and inexpensive technology can be used as a lab-on-a-chip component for initial whole blood sample preparation. Its integration into microanalytical devices that require Leukocyte enrichment will enable accelerated transition of these devices into the field for point-of-care clinical testing.
Douglas G Johns - One of the best experts on this subject based on the ideXlab platform.
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role of p38 map kinase in postcapillary venule Leukocyte adhesion induced by ischemia reperfusion injury
Pharmacological Research, 2005Co-Authors: Douglas G Johns, Zhaohui Ao, Robert N Willette, Colin H Macphee, Stephen A DouglasAbstract:Abstract Inflammation and Leukocyte activation/infiltration play a major role in the initiation and progression of cardiovascular diseases including atherosclerosis and heart failure. Acute p38 mitogen-activated protein kinase (MAPK) pathway inhibition attenuates tissue damage and Leukocyte accumulation in myocardial ischemia/reperfusion injury, although its effect on the acute phase of Leukocyte recruitment has not been elucidated. The purpose of this study was to test the hypothesis that acute treatment of rats with a selective p38 inhibitor, SB-239063, inhibits ischemia/reperfusion-induced Leukocyte-endothelial adhesion in vivo. Male Sprague–Dawley rats were treated with either SB-239063 (10 mg kg−1), dexamethasone (3 mg kg−1) or vehicle 1 h prior to ischemia. Postcapillary venules were observed microscopically in exteriorized, superfused cremaster tissue. Leukocytes were fluorescently labeled in vivo using intravenous rhodamine 6G. Leukocyte adhesion, rolling, and rolling velocities were quantitated prior to 30 min ischemia, and at several time points during a 90 min reperfusion period. Ischemia caused a 3-fold increase in adherent Leukocytes 5 min following reperfusion, a response that was maintained throughout the monitoring period (90 min) in vehicle-treated animals. SB-239063, at a dose known to inhibit p38 MAPK activity in vivo (10 mg kg−1), had no effect on ischemia/reperfusion-induced Leukocyte adhesion, the number of rolling Leukocytes, rolling velocities during the reperfusion period or adhesion molecule expression (P-, E-selectin, VCAM-1, ICAM-1). In contrast, dexamethasone completely blocked Leukocyte adhesion in response to ischemia/reperfusion, and reduced expression of E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). We conclude that p38 MAPK may not play a role in initial Leukocyte recruitment in response to ischemia/reperfusion injury, but could affect Leukocyte emigration, thereby resulting in increased Leukocyte accumulation in ischemic-reperfused tissue.
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Role of p38 MAP kinase in postcapillary venule Leukocyte adhesion induced by ischemia/reperfusion injury.
Pharmacological Research, 2005Co-Authors: Douglas G Johns, Zhaohui Ao, Robert N Willette, Colin H Macphee, Stephen A DouglasAbstract:Abstract Inflammation and Leukocyte activation/infiltration play a major role in the initiation and progression of cardiovascular diseases including atherosclerosis and heart failure. Acute p38 mitogen-activated protein kinase (MAPK) pathway inhibition attenuates tissue damage and Leukocyte accumulation in myocardial ischemia/reperfusion injury, although its effect on the acute phase of Leukocyte recruitment has not been elucidated. The purpose of this study was to test the hypothesis that acute treatment of rats with a selective p38 inhibitor, SB-239063, inhibits ischemia/reperfusion-induced Leukocyte-endothelial adhesion in vivo. Male Sprague–Dawley rats were treated with either SB-239063 (10 mg kg−1), dexamethasone (3 mg kg−1) or vehicle 1 h prior to ischemia. Postcapillary venules were observed microscopically in exteriorized, superfused cremaster tissue. Leukocytes were fluorescently labeled in vivo using intravenous rhodamine 6G. Leukocyte adhesion, rolling, and rolling velocities were quantitated prior to 30 min ischemia, and at several time points during a 90 min reperfusion period. Ischemia caused a 3-fold increase in adherent Leukocytes 5 min following reperfusion, a response that was maintained throughout the monitoring period (90 min) in vehicle-treated animals. SB-239063, at a dose known to inhibit p38 MAPK activity in vivo (10 mg kg−1), had no effect on ischemia/reperfusion-induced Leukocyte adhesion, the number of rolling Leukocytes, rolling velocities during the reperfusion period or adhesion molecule expression (P-, E-selectin, VCAM-1, ICAM-1). In contrast, dexamethasone completely blocked Leukocyte adhesion in response to ischemia/reperfusion, and reduced expression of E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). We conclude that p38 MAPK may not play a role in initial Leukocyte recruitment in response to ischemia/reperfusion injury, but could affect Leukocyte emigration, thereby resulting in increased Leukocyte accumulation in ischemic-reperfused tissue.
D N Granger - One of the best experts on this subject based on the ideXlab platform.
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Molecular determinants of shear rate-dependent Leukocyte adhesion in postcapillary venules
American Journal of Physiology-heart and Circulatory Physiology, 1993Co-Authors: Karine Bienvenu, D N GrangerAbstract:Recent studies have demonstrated that reductions in shear rate are associated with the recruitment of rolling and adherent Leukocytes in postcapillary venules. The objective of this study was to define the molecular determinants of the Leukocyte-endothelial cell adhesive interactions elicited by low venular shear rates. Three different monoclonal antibodies (MAb) were used to assess the relative contributions of CD18 (MAb R15.7), intercellular adhesion molecule 1 (ICAM-1; MAb RR1/1), and P-selectin (MAb PB1.3) to shear rate-dependent Leukocyte rolling and adherence. Erythrocyte velocity, vessel diameter, Leukocyte adherence, and Leukocyte rolling velocity were monitored in cat mesenteric venules (25-40 microns diam). Venular shear rate was varied in a stepwise fashion by graded occlusion of an arterial circuit between the femoral and superior mesenteric arteries. Shear rates were maintained at each level for a period of 2 min. The MAbs directed against either CD18 or ICAM-1, but not P-selectin, significantly attenuated the recruitment of adherent Leukocytes normally observed at low shear rates. However, the MAb against P-selectin, but not CD18 or ICAM-1, was effective in reducing the recruitment of rolling Leukocytes elicited by low shear rates. These observations indicate that shear rate-dependent recruitment of adherent Leukocytes involves an interaction between CD11/CD18 on Leukocytes and ICAM-1 on vascular endothelium, while P-selectin on endothelial cells mediates, at least part of, the recruitment of rolling Leukocytes.
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role of cd11 cd18 in shear rate dependent Leukocyte endothelial cell interactions in cat mesenteric venules
Journal of Clinical Investigation, 1991Co-Authors: M A Perry, D N GrangerAbstract:In vivo microscopy was used to assess the relationships among shear rate (and shear stress), Leukocyte rolling velocity, and Leukocyte adherence in a cat mesentery preparation. Shear rate in individual venules and arterioles of 25-35 microns diameter were varied over a wide range by graded occlusion of an arterial loop. There was a linear decline in Leukocyte rolling velocity (Vwbc) as red cell velocity (Vrbc) was reduced. The ratio Vwbc/Vrbc remained constant despite variations in shear stress from 5-25 dyn/cm2. A reduction in shear stress was associated with an increased Leukocyte adherence, particularly when Vwbc was reduced below 50 microns/s. Reduction in wall shear rate below 500 s-1 in arterioles allowed 1-3 Leukocytes to adhere per 100 microns length of vessel, while venules exposed to the same shear rates had 5-16 adherent Leukocytes. In arterioles, Leukocyte rolling was only observed at low shear rates. At shear rates less than 250 s-1 Leukocyte rolling velocity was faster in arterioles than venules, and the ratio Vwbc/Vrbc for arterioles was 0.08 +/- 0.02, which was fourfold higher than the ratio obtained in venules at similar shear rates. Pretreatment with the CD18-specific antibody (mAb) IB4 increased Leukocyte rolling velocity in venules by approximately 20 microns/s at red cell velocities below 2,000 microns/s. mAb IB4 largely prevented the Leukocyte adherence to arterioles and venules, and increased the ratio Vwbc/Vrbc observed in venules at low shear elicit a CD18-dependent adhesive interaction between Leukocytes and microvascular endothelium, and that differences in shear rates cannot explain the greater propensity for Leukocyte rolling and adhesion in venules than arterioles.
Sergey S Shevkoplyas - One of the best experts on this subject based on the ideXlab platform.
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biomimetic autoseparation of Leukocytes from whole blood in a microfluidic device
Analytical Chemistry, 2005Co-Authors: Sergey S Shevkoplyas, Tatsuro Yoshida, Mark W ItenskyAbstract:Leukocytes comprise less than 1% of all blood cells. Enrichment of their number, starting from a sample of whole blood, is the required first step of many clinical and basic research assays. We created a microfluidic device that takes advantage of the intrinsic features of blood flow in the microcirculation, such as plasma skimming and Leukocyte margination, to separate Leukocytes directly from whole blood. It consists of a simple network of rectangular microchannels designed to enhance lateral migration of Leukocytes and their subsequent extraction from the erythrocyte-depleted region near the sidewalls. A single pass through the device produces a 34-fold enrichment of the Leukocyte-to-erythrocyte ratio. It operates on microliter samples of whole blood, provides positive, continuous flow selection of Leukocytes, and requires neither preliminary labeling of cells nor input of energy (except for a small pressure gradient to support the flow of blood). This effortless, efficient, and inexpensive technology can be used as a lab-on-a-chip component for initial whole blood sample preparation. Its integration into microanalytical devices that require Leukocyte enrichment will enable accelerated transition of these devices into the field for point-of-care clinical testing.
