The role of neutrophils and platelets in a rabbit model of thromboembolic stroke.

Bednar, Martin M.; Raymond, Sheila J.; McAuliffe, Timothy L.; Lodge, Patricia A.; Gross, Cordell E.

doi:10.1161/01.str.22.1.44

Cited by 136 publications

(51 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Subjects with increased WBC count have excess risk of ischemic strokes independently of other cardiovascular risk factors [26]. Furthermore, WBC count has been shown to contribute to the initiation and further development of ischemic stroke [27,28]. Two studies showed that WBC count measured in patients during the first 24-hours after the stroke onset was significantly elevated in comparison to healthy controls [24,29].…”

Section: Discussionmentioning

confidence: 99%

Predictors of In-Hospital Mortality after Acute Ischemic Stroke in Subjects with and without Diabetes Mellitus

Papazafiropoulou¹,

Sotiropoulos²,

Skliros³

et al. 2009

TOGMJ

View full text Add to dashboard Cite

Abstract:Background: Diabetes mellitus is a well-established risk factor for ischemic stroke and is associated with increased in-hospital mortality. The aim of the present study was to determine the potential predictors of in-hospital mortality after an ischemic stroke in diabetic and nondiabetic subjects. Methods: 159 diabetic subjects (66 males / 93 females, mean age ± SD: 77.4 ± 6.4 years) and 159 non diabetic subjects (66 males / 93 females, mean age ± SD: 77.3 ± 5.2 years) hospitalized for ischemic stroke were studied. Demographic characteristics and laboratory tests on admission as well as outcome were recorded. Brain computed tomography scan was performed in all study subjects. Results: In-hospital death rates did not differ between the diabetic and the nondiabetic patients [36 (22.6%) vs. 27 (17.0%), respectively, P = 0.20]. In the diabetic study group multivariate analysis, after controlling for CRP, total cholesterol, LDL-C, urea and creatinine levels, demonstrated that death was related with WBC count (OR: 1.002, 95% CI: 1.001-1.004, P = 0.005), glucose levels (OR: 1.007, 95% CI: 1.002-1.012, P = 0.008), and UA levels (OR: 1.51, 95% CI: 1.003-2.260, P = 0.05). In the nondiabetic study group, after controlling for WBC count, CRP, total cholesterol and LDL-C levels, death was related only with glucose levels (OR: 1.016, 95% CI: 1.001-1.031, P = 0.03). Conclusions: WBC count and UA levels on hospital admission are independent predictors for in-hospital mortality in diabetic subjects with ischemic stroke. Plasma glucose levels are predictor for in-hospital mortality in both diabetic and nondiabetic subjects.

show abstract

Section: Discussionmentioning

confidence: 99%

Predictors of In-Hospital Mortality after Acute Ischemic Stroke in Subjects with and without Diabetes Mellitus

Papazafiropoulou¹,

Sotiropoulos²,

Skliros³

et al. 2009

TOGMJ

View full text Add to dashboard Cite

show abstract

“…Binding of PMN to platelets in a thrombus may facilitate immigration into thrombosed areas, wound healing, tissue repair, or protection from infection, and may contribute to the maintenance of vascular integrity, as well as to its impairment in pathological states. Platelets and PMN do indeed colocalize at sites of hemorrhage, vascular grafts, atherosclerotic lesions, and myocardial infarction (58)(59)(60)(61). Activation of PMN with platelet adhesion occurs after coronary angioplasty and has been associated with late clinical events (62).…”

Section: Discussionmentioning

confidence: 99%

Neutrophil accumulation on activated, surface-adherent platelets in flow is mediated by interaction of Mac-1 with fibrinogen bound to alphaIIbbeta3 and stimulated by platelet-activating factor.

Weber¹,

Springer²

1997

J. Clin. Invest.

349

290

View full text Add to dashboard Cite

We have studied the pathways that lead to arrest and firm adhesion of rolling PMN on activated, surface-adherent platelets. Stable arrest and adhesion strengthening of PMN on thrombin-stimulated, surface-adherent platelets in flow required distinct Ca 2 ϩ -and Mg 2 ϩ -dependent regions of Mac-1 ( ␣ M ␤ 2), and involved interactions of Mac-1 with fibrinogen, which was bound to platelets via ␣ IIb ␤ 3. Mac-1 also bound to other unidentified ligands on platelets, which were not intracellular adhesion molecule-2 (ICAM-2), heparin, or heparan-sulfate proteoglycans. This was shown by inhibition with mAbs or peptides, by treatment of platelets with heparitinase, and by using platelets with defective ␣ IIb ␤ 3 from a patient with Glanzmann thrombasthenia. Tethering of PMN on platelet ICAM-2 via LFA-1 ( ␣ L ␤ 2) was observed, which may facilitate the transition between rolling on selectins and Mac-1-dependent arrest. Arrest and adhesion strengthening was pertussis toxin sensitive and in flow was mainly induced by platelet-activating factor but not through activation of the chemokine receptor CXCR2. In stasis, spreading occurred and the CXCR2 contributed to firm adhesion. ( J.

show abstract

“…Binding of PMN to platelets immobilized in a thrombus may facilitate immigration into thrombosed areas, wound healing, tissue repair, or protection from infection, and may contribute to the maintenance of vascular integrity, as well as to its impairment in pathological states. Platelets and PMN indeed colocalize at sites of hemorrhage, vascular grafts, atherosclerotic lesions and myocardial infarction (57)(58)(59)(60). Activation of PMN and platelet adhesion occurs after coronary angioplasty and is associated with late clinical events (61).…”

Section: Involvement Of Platelet-activating Factor (Paf) and Leukotrimentioning

confidence: 99%

Effects of Oxidized Low Density Lipoprotein, Lipid Mediators and Statins on Vascular Cell Interactions

Weber¹,

Erl²,

Weber³

et al. 1999

CCLM

View full text Add to dashboard Cite

The integrin heterodimer CD11b/CD18 (␣M␤2, Mac-1, CR3) expressed on monocytes or polymorphonuclear leukocytes (PMN) is a receptor for iC3b, fibrinogen, heparin, and for intercellular adhesion molecule (ICAM)-1 on endothelium, crucially contributing to vascular cell interactions in inflammation and atherosclerosis. In this report, we summarize our findings on the effects of lipid mediators and lipid-lowering drugs. Exposure of endothelial cells to oxidized low density lipoprotein (oxLDL) induces upregulation of ICAM-1 and increases adhesion of monocytic cells expressing Mac-1. Inhibition experiments show that monocytes use distinct ligands, i.e. ICAM-1 and heparan sulfate proteoglycans for adhesion to oxLDL-treated endothelium. An albumin-transferable oxLDL activity is inhibited by the antioxidant pyrrolidine dithiocarbamate (PDTC), while 8-epi-prostaglandin F2␣ (8-epi-PGF2␣) or lysophosphatidylcholine had no effect, implicating yet unidentified radicals. Sequential adhesive and signaling events lead to the firm adhesion of rolling PMN on activated and adherent platelets, which may occupy areas of endothelial denudation. Shear-resistant arrest of PMN on thrombin-stimulated platelets in flow conditions requires distinct regions of Mac-1, involving its interactions with fibrinogen bound to platelet ␣IIb␤3, and with other platelet ligands. Both arrest and adhesion strengthening under flow are stimulated by platelet-activating factor and leukotriene B4, but not by the chemokine receptor CXCR2. We tested whether Mac-1-dependent monocyte adhesiveness is affected by inhibitors of hydroxy-methylglutaryl-Coenzyme A reductase (statins) which improve morbidity and survival of patients with coronary heart disease. As compared to controls, adhesion of isolated monocytes to endothelium ex vivo was increased in patients with hypercholesterolemia. Treatment with statins decreased total and low density lipoprotein (LDL) cholesterol plasma levels, surface expression of Mac-1, and resulted in a dramatic reduction of Mac-1-mediated monocyte adhesion to endothelium. The inhibition of monocyte adhesion was reversed by mevalonate but not LDL in vitro, indicating that isoprenoid precursors are crucial for adhesiveness of Mac-1. Such effects may crucially contribute to the clinical benefit of statins, independent of cholesterol-lowering, and may represent a paradigm for novel, anti-inflammatory mechanisms of action by this class of drugs.

show abstract

The role of neutrophils and platelets in a rabbit model of thromboembolic stroke.

Cited by 136 publications

References 52 publications

Predictors of In-Hospital Mortality after Acute Ischemic Stroke in Subjects with and without Diabetes Mellitus

Predictors of In-Hospital Mortality after Acute Ischemic Stroke in Subjects with and without Diabetes Mellitus

Neutrophil accumulation on activated, surface-adherent platelets in flow is mediated by interaction of Mac-1 with fibrinogen bound to alphaIIbbeta3 and stimulated by platelet-activating factor.

Effects of Oxidized Low Density Lipoprotein, Lipid Mediators and Statins on Vascular Cell Interactions

Contact Info

Product

Resources

About