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.

Weber, Christian; Springer, Timothy A.

doi:10.1172/jci119742

Cited by 347 publications

(310 citation statements)

References 60 publications

(39 reference statements)

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“…We studied the pathways that lead to arrest and firm adhesion of rolling PMN on activated, surface-adherent platelets (50). Stable arrest and adhesion strengthening of PMN on thrombin-stimulated, surface-adherent platelets in flow requires distinct Ca 2+ -and Mg 2+ -dependent regions of Mac-1 (αMβ2) and involves interactions of Mac-1 with fibrinogen bound to platelets via αIIbβ3.…”

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

confidence: 99%

“…Stable arrest and adhesion strengthening of PMN on thrombin-stimulated, surface-adherent platelets in flow requires distinct Ca 2+ -and Mg 2+ -dependent regions of Mac-1 (αMβ2) and involves interactions of Mac-1 with fibrinogen bound to platelets via αIIbβ3. Mac-1 also binds to unidentified ligands on platelets other than ICAM-2, heparin or heparan sulfate proteoglycans, as seen by inhibition with mAbs or peptides, treatment of platelets with heparitinase and by using platelets with defective αIIbβ3 from a patient with Glanzmann thrombasthenia (50). Tethering of PMN on platelet ICAM-2 via LFA-1 may facilitate the transition between rolling on selectins and Mac-1-dependent arrest.…”

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

confidence: 99%

“…Hence, chemoattractive lipid mediators may play a role in accumulation and adhesion strengthening of PMN on activated platelets in flow. Pretreatment of PMN with the PAF receptor antagonist UK-74,505 (51) results in a dose-dependent inhibition of PMN accumulation (50). The LTB4 receptor antagonist SC-53228 is less po-tent, while no additive effects are seen with both antagonists over UK-74,505 alone.…”

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

confidence: 99%

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

Weber¹,

Erl²,

Weber³

et al. 1999

CCLM

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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.

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

confidence: 99%

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

confidence: 99%

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

confidence: 99%

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

Weber¹,

Erl²,

Weber³

et al. 1999

CCLM

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“…In addition to allowing liaison between platelets, that receptor binds to MAC-1 receptor of leukocytes resulting in platelet-leukocyte aggregates and in white cell activation. 12 Blockade of the glycoprotein IIb/IIIa receptor may thus attenuate formation of such complexes and may reduce inflammation. In addition, activated platelets release many pro-inflammatory molecules such as sCD40L.…”

Section: Discussionmentioning

confidence: 99%

Effect of High Bolus Dose Tirofiban on the Inflammatory Response Following Percutaneous Coronary Intervention

Azar¹,

Badaoui²,

Sarkis³

et al. 2010

Clinical Cardiology

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Background: Tirofiban at the bolus dose of 10 µg/kg does not suppress the inflammatory response following percutaneous coronary intervention (PCI). This may be due to less than optimal inhibition of platelet aggregation. High bolus dose tirofiban (25 µg/kg) allows better inhibition of platelet aggregation but its anti-inflammatory effect remains unknown. Hypothesis: High bolus dose tirofiban exhibits anti-inflammatory activity. Methods: A total of 100 patients referred for PCI were randomized to receive high bolus dose tirofiban followed by a 24-h infusion or a bolus and an infusion of saline. Patients with elevated troponin or with thrombus in the culprit lesion were excluded. Inflammatory markers were measured at baseline and at 24 h. Results: Levels of soluble CD40 ligand (sCD40L) were not affected by PCI while those of interleukin-6 (IL-6) and of high sensitivity C-reactive protein (hs-CRP) significantly increased. Despite inhibiting platelet's aggregation by >90%, tirofiban did not suppress the rise of IL-6 and hs-CRP. Median (interquartile range) elevation of IL-6 was 0.6 pg/mL (−1.5-3.6) versus 0.4 pg/mL (−0.7-1.8) and that of hs-CRP was 2.1 mg/L (0.7-5.2) versus 2.4 mg/L (1-4.7) in the tirofiban and the control groups, respectively (p = ns). However, in patients with diabetes mellitus, tirofiban significantly suppressed the rise of hs-CRP by 65% (p = 0.01), but did not significantly affect the rise of IL-6. Conclusion: In low-risk patients undergoing PCI, tirofiban did not attenuate the rise of inflammatory markers. However, the significant effect in diabetics suggests that tirofiban may have anti-inflammatory activity in higher risk patients.

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“…During the inflammation process, the interaction of neutrophils with activated platelets is coordinated by an adhesion cascade [7] in which platelet P-selectin binds to P-selectin glycoprotein ligand-1 (PSGL-1) on leukocytes to promote the initial tethering of the cells and the subsequent firm adhesion is mediated by b2 integrin CD11b/ 18 (Mac-1) binding to either platelet-GPIb [8] or to fibrinogen bound to platelet GPIIb/IIIa or integrin avb3 [9].…”

Section: Introductionmentioning

confidence: 99%

Involvement of platelet glycoprotein Ib in platelet microparticle mediated neutrophil activation

Hung

Lin

et al. 2006

J Biomed Sci

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SummaryPlatelet microparticles (MPs) are membrane vesicles shed by platelets after activation, and carry antigens characteristic of intact platelets, such as glycoprotein (GP) IIb/IIIa, GPIb and P-selectin. Elevated platelet MPs have been observed in many disorders in which platelet activation is documented. Recently, platelet GPIb has been implicated in the mediation of platelet-leukocyte interaction via binding to its ligand Mac-1 on leukocyte. The role of GPIb for mediating adhesion-activation interactions between platelet MPs and leukocytes has not been clarified. In this study we investigate the role of GPIb in the interplay between platelet MPs and neutrophils. Platelet MPs were obtained from collagen-stimulated platelet-rich plasma (PRP). In a study model of neutrophil aggregation, platelet MPs can serve a bridge to support neutrophil aggregation under venous level shear stress, suggesting that platelet MPs may enhance leukocyte aggregation, which would bear clinical relevance in diseases where the platelet MPs are elevated. The level of aggregation can be reduced by GPIb blocking antibodies, AP1 and SZ2, but not by anti-CD18 mAb. The GPIb blocking antibodies also decreased platelet MP-mediated neutrophil activation, including b2 integrin expression, adherence-dependent superoxide release and platelet MP-mediated neutrophil adherence to immobilized fibrinogen. Our data provide the evidence for the involvement of GPIb-Mac-1 interaction in the cross-talk between platelet MPs and neutrophils.

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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.

Cited by 347 publications

References 60 publications

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

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

Effect of High Bolus Dose Tirofiban on the Inflammatory Response Following Percutaneous Coronary Intervention

Involvement of platelet glycoprotein Ib in platelet microparticle mediated neutrophil activation

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