کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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5949050 | 1172385 | 2012 | 8 صفحه PDF | دانلود رایگان |
Adhesive interactions between endothelial cells and leukocytes contribute to atherosclerotic plaque growth. However, mechanism(s) responsible for endothelial priming and deactivation in inflammatory diseases such as atherosclerosis are not clear.Apolipoprotein E deficient mice were generated with deficiency of P-selectin glycoprotein ligand-1 (Psgl-1â/â, ApoEâ/â). On both standard chow and Western diet, Psgl-1â/â, ApoEâ/â mice were protected against atherosclerosis compared to Psgl-1+/+, ApoEâ/â controls. Psgl-1â/â, ApoEâ/â mice also showed reduced leukocyte rolling and firm attachment on endothelial cells, however, adoptively transferred Psgl-1+/+, ApoEâ/â leukocytes into Psgl-1â/â, ApoEâ/â hosts displayed similar reduced rolling as Psgl-1â/â, ApoEâ/â leukocytes. Hematopoietic deficiency of Psgl-1 conferred resistance to the effects of interleukin-1β (IL-1β) on leukocyte rolling along with reduced circulating levels of sP-sel and sE-sel. Antibody blockade of Psgl-1 also reduced endothelial activation in response to IL-1β, eliminated leukocyte rolling, and was protective against atherosclerosis in ApoEâ/â mice. Monocyte depletion with clodronate restored the endothelial response to IL-1β in Psgl-1â/â mice. This study suggests that Psgl-1 deficiency leads to reduced atherosclerosis and adhesive interactions between endothelial cells and leukocytes by indirectly regulating endothelial responses to cytokine stimulation.
Journal: Atherosclerosis - Volume 220, Issue 1, January 2012, Pages 110-117