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Abstract: P638 DIET-INDUCED HYPERLIPIDEMIA ACTIVATES MYD88-DEPENDENT INNATE IMMUNE SIGNALING RESULTING IN INCREASED LEUKOCYTE ROLLING IN VIVO
Poster - BASIC SCIENCE - Inflammation Abstract: P638 Citation: Atherosclerosis Supplement 2009, Vol. 10, Issue 2
DIET-INDUCED HYPERLIPIDEMIA ACTIVATES MYD88-DEPENDENT INNATE IMMUNE SIGNALING RESULTING IN INCREASED LEUKOCYTE ROLLING IN VIVO A Pistea, K Olofsson, M Lindholm, A Zetterqvist, J Öhman, M Gomez, J Nilsson, H Thorlacius, H Björkbacka Dept. Of Clinical Sciences, Malmö University Hospital, Lund University, Malmo Objectives: Atherosclerosis-prone mice lacking MyD88, a key adaptor protein for innate immunity signaling initiated by Toll-like receptors and interleukin-1/-18 receptors, develop smaller plaques with less leukocyte infiltration than control mice. We hypothesized that dietinduced hyperlipidemia initiates MyD88-dependent vascular inflammation by enhancing leukocyte-endothelium interactions in vivo. Methods: Leukocyte rolling and adhesion was assessed in the femoral vessels by intravital microscopy in Myd88-/-Apoe-/- and Apoe-/- mice after 4 weeks of either normal chow or a high fat diet (HFD). Leukocyte and endothelial cell activation was studied with flow cytometry and confocal immunofluorescence microscopy. Results: Leukocyte rolling flux in the femoral vein after HFD was 4 fold higher in Apoe-/- than in Myd88-/-Apoe-/- mice (p < 0.001). HFD increased the number of circulating polymorphonuclear leukocytes (PMN) and leukocyte-platelet aggregates in Apoe-/- but not in Myd88-/-Apoe-/- mice. PMN activation, defined as increased L-selectin shedding, was higher in Apoe-/- than in Myd88/-Apoe-/- mice. However, there was no difference in endothelial activation as assessed by expression of E-selectin, P-selectin and vascular cell adhesion molecule-1. Conclusions: Increased leukocyte rolling in response to diet-induced hyperlipidemia involves innate immune activation mediated by MyD88, and relies on a MyD88-dependent neutrophilia and increased number of leukocyte-platelet aggregates. Funding: The Swedish Research Council and the Swedish Heart Lung Foundation.
DIET-INDUCED HYPERLIPIDEMIA ACTIVATES MYD88-DEPENDENT INNATE IMMUNE SIGNALING RESULTING IN INCREASED LEUKOCYTE ROLLING IN VIVO A Pistea, K Olofsson, M Lindholm, A Zetterqvist, J Öhman, M Gomez, J Nilsson, H Thorlacius, H Björkbacka Dept. Of Clinical Sciences, Malmö University Hospital, Lund University, Malmo Objectives: Atherosclerosis-prone mice lacking MyD88, a key adaptor protein for innate immunity signaling initiated by Toll-like receptors and interleukin-1/-18 receptors, develop smaller plaques with less leukocyte infiltration than control mice. We hypothesized that dietinduced hyperlipidemia initiates MyD88-dependent vascular inflammation by enhancing leukocyte-endothelium interactions in vivo. Methods: Leukocyte rolling and adhesion was assessed in the femoral vessels by intravital microscopy in Myd88-/-Apoe-/- and Apoe-/- mice after 4 weeks of either normal chow or a high fat diet (HFD). Leukocyte and endothelial cell activation was studied with flow cytometry and confocal immunofluorescence microscopy. Results: Leukocyte rolling flux in the femoral vein after HFD was 4 fold higher in Apoe-/- than in Myd88-/-Apoe-/- mice (p < 0.001). HFD increased the number of circulating polymorphonuclear leukocytes (PMN) and leukocyte-platelet aggregates in Apoe-/- but not in Myd88-/-Apoe-/- mice. PMN activation, defined as increased L-selectin shedding, was higher in Apoe-/- than in Myd88/-Apoe-/- mice. However, there was no difference in endothelial activation as assessed by expression of E-selectin, P-selectin and vascular cell adhesion molecule-1. Conclusions: Increased leukocyte rolling in response to diet-induced hyperlipidemia involves innate immune activation mediated by MyD88, and relies on a MyD88-dependent neutrophilia and increased number of leukocyte-platelet aggregates. Funding: The Swedish Research Council and the Swedish Heart Lung Foundation.