Presentation is loading. Please wait.

Presentation is loading. Please wait.

Osama M. El-Sayed, BS, Nicholas A. Dewyer, MD, Catherine E

Published byLanny Pranoto Modified over 5 years ago

Similar presentations

Presentation on theme: "Osama M. El-Sayed, BS, Nicholas A. Dewyer, MD, Catherine E"— Presentation transcript:

1 Intact Toll-like receptor 9 signaling in neutrophils modulates normal thrombogenesis in mice 
Osama M. El-Sayed, BS, Nicholas A. Dewyer, MD, Catherine E. Luke, LVT, Megan Elfline, MS, Adriana Laser, MD, Cory Hogaboam, PhD, Steven L. Kunkel, PhD, Peter K. Henke, MD  Journal of Vascular Surgery  Volume 64, Issue 5, Pages e1 (November 2016) DOI: /j.jvs Copyright © 2015 Society for Vascular Surgery Terms and Conditions

2 Fig 1 A, Larger thrombi are present in stasis venous thrombosis (VT) at 6 hours and 2 days in Toll-like receptor 9 knockout (Tlr9−/−) mice compared with wild-type (WT) mice (n = 6-10) but not in nonstasis (electrolytic induction model [EIM]) Tlr9−/− compared with WT (n = 4-6). B, Thrombus interleukin 1-α (IL-1α) was reduced in Tlr9−/− mice compared with WT controls (n = 5). C, Thrombus uric acid concentration was increased in Tlr9−/− mice compared with WT controls (n = 6-7). D, Thrombus TUNEL+ cell counts in five high-power fields (5hpf) are shown. At 2 days, Tlr9−/− thrombi contained an increased number of TUNEL+ cells compared with WT controls (n = 4). Histology representative photos with TUNEL+ cells fluorescing green and 4′,6-diamidino-2-phenylindole (DAPI) fluorescing blue (magnification ×100; scale bar = 100 μm) in WT and Tlr9−/− thrombus (arrows denote dual-staining cells). E, Activated polymorphonuclear neutrophils (PMNs; Ly6G+) were increased in Tlr9−/− thrombi compared with WT thrombi (n = 5). F, Two histology image examples show greater Ly6G+ cells labeled in brown (arrows) in Tlr9−/− and WT (magnification ×100; scale bar = 100 μm). Data are mean ± standard deviation. ∗P < .05. Journal of Vascular Surgery  , e1DOI: ( /j.jvs ) Copyright © 2015 Society for Vascular Surgery Terms and Conditions

3 Fig 2 Venous thrombi in Toll-like receptor 9 knockout (Tlr9−/−) mice have increased neutrophil extracellular trap (NET) markers by Western immunoblotting and less antithrombogenic inhibitor compared with wild-type (WT) controls. A, Citrullinated histones (H3-Cit). B, Peptidylarginine deiminase 4 (PAD4). C, Elastase. D, Tissue factor pathway inhibitor (TFPI; n = 4-6). Data are mean ± standard deviation. ∗P < .05. Journal of Vascular Surgery  , e1DOI: ( /j.jvs ) Copyright © 2015 Society for Vascular Surgery Terms and Conditions

4 Fig 3 A, The number of neutrophil extracellular trap-positive (NET+) polymorphonuclear neutrophils (PMNs) was increased in Toll-like receptor 9 knockout (Tlr9−/−) mice compared with wild-type (WT) controls (n = 4-6). B, NET immunofluorescence histograph examples show costaining with PMNs of 4′,6-diamidino-2-phenylindole (DAPI), citrullinated histone (cit-H3), and Ly6G (arrows; magnification ×1000). C, Deoxyribonuclease (DNAse) I treatment (Tx) did not affect stasis venous thrombosis (VT) in WT or Tlr9−/− mice at 2 days (n = 6-8). D, Thrombus size was not altered in stasis VT in peptidylarginine deiminase 4 knockout (PAD4−/−) mice compared with WT mice (n = 6-8). Data are mean ± standard deviation. ∗P < .05. Journal of Vascular Surgery  , e1DOI: ( /j.jvs ) Copyright © 2015 Society for Vascular Surgery Terms and Conditions

5 Fig 4 Cellular polymorphonuclear neutrophil (PMN) processes in thrombogenesis. A, PMN antibody depletion (treatment [Tx]) significantly reduced venous thrombus (VT) size in Toll-like receptor 9 knockout (Tlr9−/−) mice compared with wild-type (WT) controls (n = 5). B-D, Thrombus elastase (B) and citrullinated histones (cit-H3; C) were reduced in Tlr9−/− mice with PMN depletion, whereas tissue factor pathway inhibitor (TFPI; D) was increased (n = 4-6). IgG, Immunoglobulin G. E, Intrathrombus PMNs were reduced in Tlr9−/− mice with treatment (n = 3-5). Example of hematoxylin and eosin-stained thrombus sections (magnification ×200; arrows indicate PMNs). Data are mean ± standard deviation. ∗P < .05. Journal of Vascular Surgery  , e1DOI: ( /j.jvs ) Copyright © 2015 Society for Vascular Surgery Terms and Conditions

6 Supplementary Fig (online only)
Very early (6 hours) thrombi in Toll-like receptor 9 knockout (Tlr9−/−) mice have altered size and composition. A, Thrombus citrullinated histones (H3-Cit) were not significantly different between wild-type (WT) and Tlr9−/− thrombi. B, Thrombus elastase was greater in Tlr9−/− than in WT mice. C, Less tissue factor pathway inhibitor (TFPI) was present in Tlr9−/− compared with WT thrombi (n = 5-6). Data are mean ± standard deviation. ∗P < .05. Journal of Vascular Surgery  , e1DOI: ( /j.jvs ) Copyright © 2015 Society for Vascular Surgery Terms and Conditions

Download ppt "Osama M. El-Sayed, BS, Nicholas A. Dewyer, MD, Catherine E"

Similar presentations

Interruption of spinal cord microglial signaling by alpha-2 agonist dexmedetomidine in a murine model of delayed paraplegia  Marshall T. Bell, MD, Viktor.

Interruption of spinal cord microglial signaling by alpha-2 agonist dexmedetomidine in a murine model of delayed paraplegia  Marshall T. Bell, MD, Viktor.
Experimental pulmonary embolism: Effects of the thrombus and attenuation of pulmonary artery injury by low-molecular-weight heparin  John E. Rectenwald,

Experimental pulmonary embolism: Effects of the thrombus and attenuation of pulmonary artery injury by low-molecular-weight heparin  John E. Rectenwald,
Vein wall re-endothelialization after deep vein thrombosis is improved with low- molecular-weight heparin  Daria K. Moaveni, MD, Erin M. Lynch, MS, Cathy.

Vein wall re-endothelialization after deep vein thrombosis is improved with low- molecular-weight heparin  Daria K. Moaveni, MD, Erin M. Lynch, MS, Cathy.
Accelerated aneurysmal dilation associated with apoptosis and inflammation in a newly developed calcium phosphate rodent abdominal aortic aneurysm model 

Accelerated aneurysmal dilation associated with apoptosis and inflammation in a newly developed calcium phosphate rodent abdominal aortic aneurysm model 
Jeanwan Kang, MD, Hassan Albadawi, MD, Patrick J. Casey, MD, Thomas A

Jeanwan Kang, MD, Hassan Albadawi, MD, Patrick J. Casey, MD, Thomas A
Reduced hind limb ischemia-reperfusion injury in Toll-like receptor-4 mutant mice is associated with decreased neutrophil extracellular traps  Rahmi Oklu,

Reduced hind limb ischemia-reperfusion injury in Toll-like receptor-4 mutant mice is associated with decreased neutrophil extracellular traps  Rahmi Oklu,
Ulka Sachdev, MD, Xiangdong Cui, MS, Edith Tzeng, MD 

Ulka Sachdev, MD, Xiangdong Cui, MS, Edith Tzeng, MD 
Yi-kuan Chen, MD, Xue-mei Jiang, MSc, Jian-ping Gong, MD 

Yi-kuan Chen, MD, Xue-mei Jiang, MSc, Jian-ping Gong, MD 
Elevation of hemopexin-like fragment of matrix metalloproteinase-2 tissue levels inhibits ischemic wound healing and angiogenesis  April E. Nedeau, MD,

Elevation of hemopexin-like fragment of matrix metalloproteinase-2 tissue levels inhibits ischemic wound healing and angiogenesis  April E. Nedeau, MD,
Pharmacologic blockade and genetic deletion of androgen receptor attenuates aortic aneurysm formation  John P. Davis, MD, Morgan Salmon, PhD, Nicolas.

Pharmacologic blockade and genetic deletion of androgen receptor attenuates aortic aneurysm formation  John P. Davis, MD, Morgan Salmon, PhD, Nicolas.
Perivascular innate immune events modulate early murine vein graft adaptations  Binh T. Nguyen, MD, Peng Yu, MD, Ming Tao, MD, Shuai Hao, BS, Tianyu Jiang,

Perivascular innate immune events modulate early murine vein graft adaptations  Binh T. Nguyen, MD, Peng Yu, MD, Ming Tao, MD, Shuai Hao, BS, Tianyu Jiang,
Transglutaminase 3 Protects against Photodamage

Transglutaminase 3 Protects against Photodamage
Potential role of erythropoietin receptors and ligands in attenuating apoptosis and inflammation in critical limb ischemia  Dhiraj Joshi, MD, MRCS, David.

Potential role of erythropoietin receptors and ligands in attenuating apoptosis and inflammation in critical limb ischemia  Dhiraj Joshi, MD, MRCS, David.
Gale Tang, MD, David N. Charo, Rong Wang, PhD, Israel F

Gale Tang, MD, David N. Charo, Rong Wang, PhD, Israel F
Prevention of the second stage of epithelial loss is a potential novel treatment for bronchiolitis obliterans  Yunge Zhao, MD, PhD, John F. Steidle, BA,

Prevention of the second stage of epithelial loss is a potential novel treatment for bronchiolitis obliterans  Yunge Zhao, MD, PhD, John F. Steidle, BA,
Tamoxifen up-regulates catalase production, inhibits vessel wall neutrophil infiltration, and attenuates development of experimental abdominal aortic.

Tamoxifen up-regulates catalase production, inhibits vessel wall neutrophil infiltration, and attenuates development of experimental abdominal aortic.
Effect of blocking platelet activation with AZD6140 on development of abdominal aortic aneurysm in a rat aneurysmal model  Jianping Dai, MD, PhD, Liliane.

Effect of blocking platelet activation with AZD6140 on development of abdominal aortic aneurysm in a rat aneurysmal model  Jianping Dai, MD, PhD, Liliane.
Circulating anti-β2-glycoprotein I antibodies of peripheral arterial disease patients trigger a genomic overexpression of Toll-like receptor 4 in endothelial.

Circulating anti-β2-glycoprotein I antibodies of peripheral arterial disease patients trigger a genomic overexpression of Toll-like receptor 4 in endothelial.
Michael A. Rosenbaum, MD, Pinaki Chaudhuri, PhD, Linda M. Graham, MD 

Michael A. Rosenbaum, MD, Pinaki Chaudhuri, PhD, Linda M. Graham, MD 
Effect of DNase I treatment and neutrophil depletion on acute limb ischemia-reperfusion injury in mice  Hassan Albadawi, MD, Rahmi Oklu, MD, PhD, Rita.

Effect of DNase I treatment and neutrophil depletion on acute limb ischemia-reperfusion injury in mice  Hassan Albadawi, MD, Rahmi Oklu, MD, PhD, Rita.

Similar presentations

Ads by Google