Raised Plasma Soluble P-Selectin in Peripheral Arterial Occlusive Disease Enhances Leukocyte Adhesion

Woollard, Kevin J.; Kling, Dorothée; Kulkarni, Suhasini; Dart, Anthony M.; Jackson, Shaun P.; Chin-Dusting, Jaye

doi:10.1161/01.res.0000199295.14073.69

Cited by 55 publications

(55 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The pivotal role of P-selectin is emphasized by the observations that even soluble P-selectin, shed from the activated platelets and endothelium, stimulates leukocytes to produce tissue factor 123 and to adhere. 124 Mice overexpressing soluble P-selectin show many aspects of prothrombotic state 125 and chronic inflammation (J. Kisucka and D.D.W., unpublished observations).…”

Section: Platelet-vessel Wall Interactionsmentioning

confidence: 99%

The vessel wall and its interactions

Wagner

Frenette²

2008

Blood

310

300

View full text Add to dashboard Cite

Historical overviewThe interactions of leukocytes and platelets with the vessel wall, such as occur in inflammation, are highly dynamic and often transient. The development of intravital microscopy was the spark that allowed real-time observations of blood cells in live animals, and led to the detection and molecular analyses of their interactions with the vessel wall. Rudolph Wagner first published in 1839 a description of leukocytes interacting with the vessel wall. 1 In blood vessels of the webbed feet of a grass frog, he observed that leukocytes (then called lymph-corpuscles) in venules were moving in close contact with the vessel wall, and more slowly than other blood cells. The drawing in Figure 1 likely represents the first depiction of rolling leukocytes; we now know that leukocytes roll constitutively in venules of the skin.A few years later the frog-this time its spread tongue-was again central to another milestone microscopic observation. Augustus Waller noted that the trauma caused by the pins and the long exposure to ambient air produced a tongue irritation that triggered the adhesion of lymph-corpuscles onto the vessels of the microcirculation. He also noted that as time passed more of them "escaped" into the surrounding tissue while scarcely any red blood cells (RBCs) could be seen outside the vessel. Waller remarked on "the restorative power of blood which immediately closes the aperture" formed by the extravasating leukocytes and proposed that pus has its origin from these colorless extravasated corpuscles. 2 It took 40 years for defined theories to attempt to explain what initiates these inflammatory responses. In his Lectures on General Pathology, Julius Cohnheim stated "we have here to deal with a molecular change of the vessel walls. . . comprised under the notion and name of inflammation." 3 Cohnheim attributed everything to alterations in the endothelium and noted that inflammatory changes did not affect blood as the vessel wall could be modified even if blood were replaced by saline before ligation. In contrast, at about the same time, Elie Metchnikoff concentrated on "the fundamental importance of phagocytosis in inflammation." In this phagocytic theory of inflammation, he suggested that phagocytes were crucial to destroy the "irritant bodies." 4 Although Metchnikoff stated that "inflammation may occur without any intervention of the blood vessels," he hinted at the need for leukocyte activation as "these cells are in the first place affected by various substances which posses an attraction for them." Clearly, these brilliant scientists were equally right as it is now known that both endothelial and leukocyte activation are key to the inflammatory response.Following vascular injury, the rapid coalescence of blood platelets into forming thrombi was observed by intravital microscopy in the late 1800s (reviewed in Jackson 5 ). The adhesion of platelets to presumably intact but stimulated endothelium was documented only in 1970 by Begent and Born. 6 After ADP application to the outside of a ...

show abstract

Section: Platelet-vessel Wall Interactionsmentioning

confidence: 99%

The vessel wall and its interactions

Wagner

Frenette²

2008

Blood

310

300

View full text Add to dashboard Cite

show abstract

“…This step occurs through at least 2 mechanisms: chemokine-triggered activation of leukocyte ␤1 and ␤2 integrins, which bind to their coun- Tables I and II]); and, secondly, by selectin-dependent activation of ␤2 integrins on rolling leukocytes (primarily neutrophils), 9,10 although the importance of this mechanisms for monocyte recruitment has yet to be studied. 11 The chemokines implicated in leukocyte recruitment in animal models of atherosclerosis include monocyte chemoattractant protein (MCP)-1 (CCL2), MCP-2 (CCL8), KC (CXCL1), MIP-1␣ (CCL3), MIP-1␤ (CCL4), RANTES (CCL5), and fractalkine (CX3CL1), although this list is likely to expand 4,5 (Table 2). Certain chemokines have been shown to bind to endothelium and can be presented on the cell surface by glycosaminoglycans or syndecan-1 and -2 and trigger leukocyte arrest.…”

Section: Adhesion Pathways That Regulate Mononuclear Leukocyte Transmmentioning

confidence: 99%

Endothelial-Dependent Mechanisms of Leukocyte Recruitment to the Vascular Wall

Rao

Yang

García‐Cardeña

et al. 2007

Circulation Research

353

271

View full text Add to dashboard Cite

Abstract-Inflammation is a fundamental process that protects organisms by removing or neutralizing injurious agents. A key event in the inflammatory response is the localized recruitment of various leukocyte subsets. Here we address the cellular and regulatory mechanisms of leukocyte recruitment to the vessel wall in cardiovascular disease and discuss our evolving understanding of the role of the vascular endothelium in this process. The vascular endothelium is the continuous single-cell lining of the cardiovascular system that forms a critical interface between the blood and its components on one side and the tissues and organs on the other. It is heterogeneous and has many synthetic and metabolic functions including secretion of platelet-derived growth factor, von Willebrand factor, prostacyclin, NO, endothelin-1, and chemokines and the expression of adhesion molecules. It also acts as a nonthrombogenic and selective permeable barrier. Endothelial cells also interact closely with the extracellular matrix and with adjacent cells including pericytes and smooth muscle cells within the vessel wall. A central question in vascular biology is the role of the endothelium in the initiation of inflammatory response, the extent of its "molecular conversations" with recruited leukocytes, and its influence on the extent and/or outcome of this response. (Circ Res. 2007;101:234-247.)

show abstract

“…15,[29][30][31][32] The central hypothesis of our study was that this might occur also in vivo, in animals that shed P-selectin at an increased rate, impacting their susceptibility to vascular disease.…”

Section: Discussionmentioning

confidence: 99%

“…51 Presence of elevated sP-selectin in plasma of patients with peripheral arterial disease has been shown to induce the activation of leukocytes as detected by ␣ M ␤ 2 (Mac-1) activation, an integrin involved in leukocyte adhesion, and to enhance leukocyte adhesion on the fibrinogen or platelet monolayer in a shear-dependent manner. 15 The signaling produced by sP-selectin binding to leukocyte PSGL-1 is similar to that produced by its membrane-bound form. 15 Wang et al 31 also found that sP-selectin partially restores impaired leukocyte adhesion and peritoneal accumulation in stimulated P-selectin-deficient mice.…”

Section: Increased Levels Of Sp-selectin Accelerate Atherosclerosismentioning

confidence: 99%

“…10 Soluble P-selectin (sP-selectin) has been proposed as a useful biomarker in various pathologic states in which platelets and/or endothelial cells are activated. It is elevated in several conditions, including hyperlipidemia, 11 hypertension, 12 ischemic heart disease, 13 atherosclerosis, 14 and in patients with vascular disorders such as peripheral arterial occlusive disease 15 and postangioplasty restenosis. 16 Ridker et al 17 showed that in apparently healthy women, elevated baseline levels of sP-selectin were associated with an increased risk of future myocardial infarction, stroke, and cardiovascular death.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Elevated levels of soluble P-selectin in mice alter blood-brain barrier function, exacerbate stroke, and promote atherosclerosis

Kisucka

Chauhan

Zhao

et al. 2009

Blood

View full text Add to dashboard Cite

Cerebrovascular and cardiovascular diseases are a major cause of morbidity and mortality. Soluble P-selectin (sP-selectin) is a biomarker for platelet/endothelial activation and is considered a risk factor for vascular disease. sP-selectin enhances procoagulant activity by inducing leukocyte-derived microparticle production and promotes activation of leukocyte integrins. However, it is not known whether it directly contributes to vascular complications. We investigated the effect of increased levels of sP-selectin on bloodbrain barrier (BBB) function, stroke outcome, and atherosclerosis by comparing wild-type mice with P-sel ⌬CT/⌬CT mice in which the endogenous P-selectin gene was replaced with a mutant that produces abnormally high plasma levels of sP-selectin. P-sel ⌬CT/⌬CT mice presented several abnormalities, including (1) higher BBB permeability, with 25% of the animals showing differential permeability between the right and left hemispheres;(2) altered social behavior with increased aggression; (3) larger infarcts in the middle cerebral artery occlusion ischemic stroke model; and (4) increased susceptibility to atherosclerotic, macrophage-rich lesion development in both male and female mice on the apoE ؊/؊ genetic background. Thus, elevated sP-selectin is not only a biomarker for vascular disease, but also may contribute directly to atherosclerosis and cerebrovascular complications. (Blood. 2009;113:6015-6022)

show abstract

Raised Plasma Soluble P-Selectin in Peripheral Arterial Occlusive Disease Enhances Leukocyte Adhesion

Cited by 55 publications

References 41 publications

The vessel wall and its interactions

The vessel wall and its interactions

Endothelial-Dependent Mechanisms of Leukocyte Recruitment to the Vascular Wall

Elevated levels of soluble P-selectin in mice alter blood-brain barrier function, exacerbate stroke, and promote atherosclerosis

Contact Info

Product

Resources

About