Minimal Platelet Deposition and Activation in Models of Injured Vessel Wall Ensure Optimal Neutrophil Adhesion Under Flow Conditions

Zwaginga, Jaap‐Jan; Torres, H. I. Gallardo; Lammers, Jan-Willem; Sixma, Jan J.; Koenderman, Leo; Kuijper, P. H. M.

doi:10.1161/01.atv.19.6.1549

Cited by 28 publications

(21 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In fact, P-selectin expressed by surface-adherent activated platelets has been demonstrated to trigger significant leukocyte recruitment under flow even at a low density of surface coverage. 23 We observed here that, together with leukocytes, substantial numbers of platelets attached to inflamed HUVEC after exposure to arterial shear stress. Importantly, leukocyte adhesion strictly colocalized with platelet adhesion, whereas few leukocytes were recruited to areas devoid of adherent platelets.…”

Section: Discussionmentioning

confidence: 56%

Chemokine Fractalkine Mediates Leukocyte Recruitment to Inflammatory Endothelial Cells in Flowing Whole Blood

et al. 2007

View full text Add to dashboard Cite

Background-The membrane-bound chemokine fractalkine (CX 3 CL1) is expressed on various cell types such as activated endothelial cells and has been implicated in the inflammatory process of atherosclerosis. The aim of the present study was to dissect the role of fractalkine in leukocyte recruitment to inflamed endothelium under arterial shear forces. Methods and Results-With the use of immunofluorescence and laminar flow assays, the present study shows that human umbilical vein endothelial cells stimulated with tumor necrosis factor-␣ and interferon-␥ abundantly express CX 3 CL1 and promote substantial leukocyte accumulation under arterial flow conditions. In the presence of high shear, firm adhesion of leukocytes to inflamed endothelial cells is reduced by Ϸ40% by a function-blocking anti-fractalkine antibody or by an antibody directed against the fractalkine receptor (CX 3 CR1). With the use of intravital video-fluorescence microscopy we demonstrate that inhibition of fractalkine signaling attenuates leukocyte adhesion to the atherosclerotic carotid artery of apolipoprotein E-deficient mice, which suggests that the CX 3 CL1-CX 3 CR1 axis is critically involved in leukocyte adhesion to inflamed endothelial cells under high shear forces both in vitro and in vivo. Surprisingly, platelets were strictly required for fractalkine-induced leukocyte adhesion at high shear rates. Correspondingly, specific inhibition of platelet adhesion to inflamed endothelial cells also significantly reduced leukocyte accumulation. We show that both soluble and membrane-bound fractalkine induces platelet degranulation and subsequent surface expression of P-selectin, which thereby promotes direct platelet-leukocyte interaction.

show abstract

Section: Discussionmentioning

confidence: 56%

Chemokine Fractalkine Mediates Leukocyte Recruitment to Inflammatory Endothelial Cells in Flowing Whole Blood

et al. 2007

View full text Add to dashboard Cite

show abstract

“…41,42 In a recent study, we have shown that the mural thrombus in human atherosclerotic aneurysms is a site of storage and release of MMP-9 and that polymorphonuclear leukocytes trapped within the thrombus are the main cellular source of this MMP-9. 22 Recent luminal clots are sites of platelet deposition 43 and fibrin-fibronectin copolymerization, 44 and represent an optimal substrate for PMN adhesion. In the present work, we have extended these data using an ex vivo approach to study proteases bound to and released by the mural thrombus in human aneurysms.…”

Section: Discussionmentioning

confidence: 99%

Role of Leukocyte Elastase in Preventing Cellular Re-Colonization of the Mural Thrombus

Fontaine

Touat

Mtairag

et al. 2004

The American Journal of Pathology

123

138

View full text Add to dashboard Cite

“…Platelet P-selectin guarantees the access of leukocytes to perivascular tissues even when dying or severely damaged endothelial cells fail to sustain leukocyte rolling and adhesion. 15,16 Indeed, endothelial cells surrounding the lesion release signals that amplify the expression of P-selectin on adhering platelets. 17 The P-selectin-dependent interaction of neutrophils and platelets amplifies mutually, promoting the exchange of metabolites and protecting released molecules from plasma inhibitors.…”

Section: Introductionmentioning

confidence: 99%

Neutrophils phagocytose activated platelets in vivo: a phosphatidylserine, P-selectin, and β2 integrin–dependent cell clearance program

Maugeri

Rovere‐Querini

Evangelista

et al. 2009

Blood

129

153

View full text Add to dashboard Cite

Activated platelets express ligands, which are recognized by counterreceptors on neutrophils. Here, we show that the ensuing cell-to-cell interaction programs neutrophil phagocytic function, resulting in activated platelet clearance. Neutrophils that have internalized platelets circulate in the blood of patients with acute myocardial infarction, and the extent of platelet clearance correlates with expression of platelet activation, including P-selectin. Activated platelets injected intravenously in experimental animals are detectable in circulating neutrophils 60 minutes after, and within 3 hours, more than 70% circulating neutrophils have internalized platelets. Platelet clearance comprises 2 events: adhesion to neutrophils, which requires divalent cations and depends on P-selectin, on the P-selectin glycoprotein ligand-1 (PSGL-1), and on the CD11b/CD18 ␤2 integrin; and internalization, which is abrogated by the phosphatidylserine-binding protein annexin A5. Adhesion to platelets causes neutrophil degranulation and is blocked by antibodies specific for P-selectin and PSGL-1, either in a synthetic medium in vitro or in the whole blood, therefore in the presence of a physiologic array of plasma cofactors and opsonins. The data suggest that the interaction between circulating platelets and neutrophils influences innate immune functions, possibly contributing to regulate vascular inflammation. IntroductionNeutrophils are recruited to inflamed sites, where they are required for microbial clearance. Neutrophil recruitment is a multistep process, which comprises initial tethering and rolling along the vessel wall, firm adhesion to endothelial cells, and eventual extravasation. It involves consecutively various adhesion molecules, including selectins and ␤2 integrins. [1][2][3][4] Granules of endothelial cells (Weibel-Palade bodies) and of platelets (␣-granules) contain P-selectin. Inflammatory stimuli cause its translocation at the endothelial cell surface. The interaction with the counterreceptor, PSGL-1, prompts leukocyte tethering and rolling and initiates the second phase of the process, firm adhesion. During these events, integrins shift to an active conformation. [5][6][7] Integrin activation depends on the signaling cascade downstream the P-selectin/PSGL-1 interaction. [8][9][10] Platelets adhere and are activated at sites of vascular injury: there, they produce a releasate, some contents of which penetrate and/or interact biochemically with neutrophils. This includes unprocessed free arachidonic acid which can then be transformed into leukotriene A4 and B4. 11-14 Furthermore, activated platelets express P-selectin. Platelet P-selectin guarantees the access of leukocytes to perivascular tissues even when dying or severely damaged endothelial cells fail to sustain leukocyte rolling and adhesion. 15,16 Indeed, endothelial cells surrounding the lesion release signals that amplify the expression of P-selectin on adhering platelets. 17 The P-selectin-dependent interaction of neutrophils and platelets amplifies mut...

show abstract

Minimal Platelet Deposition and Activation in Models of Injured Vessel Wall Ensure Optimal Neutrophil Adhesion Under Flow Conditions

Cited by 28 publications

References 23 publications

Chemokine Fractalkine Mediates Leukocyte Recruitment to Inflammatory Endothelial Cells in Flowing Whole Blood

Chemokine Fractalkine Mediates Leukocyte Recruitment to Inflammatory Endothelial Cells in Flowing Whole Blood

Role of Leukocyte Elastase in Preventing Cellular Re-Colonization of the Mural Thrombus

Neutrophils phagocytose activated platelets in vivo: a phosphatidylserine, P-selectin, and β2 integrin–dependent cell clearance program

Contact Info

Product

Resources

About