Novel role of the membrane-bound chemokine fractalkine in platelet activation and adhesion

Schäfer, Andreas; Schulz, Christian; Eigenthaler, Martin; Fraccarollo, Daniela; Kobsar, Anna; Gawaz, Meinrad; Ertl, Georg; Walter, Ulrich; Bauersachs, Johann

doi:10.1182/blood-2002-10-3260

Cited by 128 publications

(101 citation statements)

References 48 publications

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“…It is feasible that platelet activation and formation of platelet-leukocyte complexes is directed by a number of chemokines, since SDF-1, monocyte-derived chemokine (MDC, CCL22), thymus and activation-regulated cytokine (TARC, CCL17) and fractalkine can activate platelets in the presence of ADP (Abi-Younes et al, 2000Kowalska et al, 2000;Schafer et al, 2004) via their receptors CXCR4, CCR1, CCR3, CCR4 and CX3CR1 (Clemetson et al, 2000;Schafer et al, 2004). Platelet activation by chemokines in the presence of low levels of ADP (insufficient alone to cause aggregation) is a very rapid process, resulting in near maximal activation within 5 s of stimulation.…”

Section: Leukocyte Recruitment and Activation: Influence Of Plateletsmentioning

confidence: 99%

Novel uses for anti‐platelet agents as anti‐inflammatory drugs

Pitchford

2007

British J Pharmacology

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An alteration in the character and function of platelets is manifested in patients with inflammatory diseases, and these alterations have been dissociated from the well‐characterized involvement of platelets in thrombosis and haemostasis. Recent evidence reveals platelet activation is sometimes critical in the development of inflammation. The mechanisms by which platelets participate in inflammation are diverse, and offer numerous opportunities for future drug intervention. There is now acceptance that platelets act as innate inflammatory cells in immune responses, with roles as sentinel cells undergoing surveillance, responding to microbial invasion, orchestrating leukocyte recruitment, and migrating through tissue, causing damage and influencing repair processes in chronic disease. Some of these processes are targeted by drugs that are being developed to target platelet participation in atherosclerosis. The actions of platelets therefore influence the pathogenesis of diverse inflammatory diseases in various body compartments, encompassing parasitic and bacterial infection, allergic inflammation (especially asthma and rhinitis), and non‐atopic inflammatory conditions, for example, chronic obstructive pulmonary disease (COPD), rheumatoid arthritis (RA), inflammatory bowel disease (IBD) and atherosclerosis. This review will first discuss the evidence for platelet activation in these various inflammatory diseases, and secondly discuss the mechanisms by which this pathogenesis occurs and the various anti‐platelet agents which have been developed to combat platelet activation in atherosclerosis and their potential future use for the treatment of other inflammatory diseases.British Journal of Pharmacology (2007) 152, 987–1002; doi:10.1038/sj.bjp.0707364; published online 2 July 2007

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Section: Leukocyte Recruitment and Activation: Influence Of Plateletsmentioning

confidence: 99%

Novel uses for anti‐platelet agents as anti‐inflammatory drugs

Pitchford

2007

British J Pharmacology

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“…The molecular pairs allowing adhesion of platelets to endothelium include Pselectin glycoprotein ligand 1/P-selectin, GPIb␣/von Willebrand factor, GPIb␣/P-selectin, and GPIIb/IIIa/fibrinogen/ ICAM-1, respectively (47). Recently, EC-derived fractalkine has also been show to contribute to platelet activation and adhesion (48). Activated platelets produce massive amounts of proinflammatory mediators and cross-talk with and activate different cells; in turn, platelets are activated by EC-derived proinflammatory substances binding to cognate receptors on the platelets' surface (49,50).…”

Section: Endothelial-platelet Interactionsmentioning

confidence: 99%

Immune Regulation by Microvascular Endothelial Cells: Directing Innate and Adaptive Immunity, Coagulation, and Inflammation

Danese¹,

Dejana

Fiocchi

2007

The Journal of Immunology

258

203

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An effective immune response depends not only on the proper activation, regulation, and function of immune cells, but also on their distribution and retention in diverse tissue microenvironments where they encounter a number of stimuli and other cell types. These activities are mediated by endothelial cells, which form specialized microcirculatory networks used by immune cells under both physiological and pathological circumstances. Endothelial cells represent a highly heterogeneous population of cells with the ability to interact with and modulate the function of immune cells. This review is focused on the role of microvascular endothelial cells in innate and adaptive immunity, inflammation, coagulation, angiogenesis, and the therapeutic implications of targeting endothelial cells in selected autoimmune and chronic inflammatory disorders.

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“…46 Fractalkine is a special chemokine that as a transmembrane protein function as an efficient EC adhesion molecules for monocytes and T cells (by an integrinindependent mechanism) and on cleavage by specific metalloproteases becomes soluble fractalkine, operating as chemoattractant for these cells. 47 Recently, it was reported that the EC membrane-bound fractalkine has a role in platelet activation and adhesion; 48 moreover, in early atherosclerosis, activated platelets, using a P-selectin mechanism, secrete and deliver RANTES and PF4 chemokines to the EC surface, enhancing monocyte recruitment by activated endothelium. 46 The large collection of chemokines advocates for the complexity of the process involved in the efficient and specific recruitment of inflammatory cells to the site of plaque formation.…”

Section: Expression Of New Cell Adhesion Moleculesmentioning

confidence: 99%

Implications of Early Structural-Functional Changes in the Endothelium for Vascular Disease

Simionescu¹

2007

ATVB

229

152

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Abstract-By location, between the blood and tissues and the multiple functions, the endothelial cells (ECs) play a major role in securing body homeostasis. The ECs sense all variations occurring in the plasma and interstitial fluid, and respond (function of intensity), initially by modulation of their constitutive functions, then by dysfunction, expressed by temporarily altered functions and a phenotypic shift, and ultimately by injury/death. In dyslipidemia/hyperglycemia, the initial response of EC is the modulation of 2 constitutive functions: permeability and biosynthesis. Increased transcytosis of plasma ␤-lipoproteins leads to their accumulation within the hyperplasic basal lamina, interaction with matrix proteins, and conversion to modified and reassembled lipoproteins (MRL). This generates a multipart inflammatory process and EC dysfunction characterized by expression of new cell adhesion molecules and MCP-1 that trigger T-lymphocytes and monocyte recruitment, diapedesis, and homing within the subendothelium where activated macrophages become foam cells. The latter, together with the subendothelial accrual of MRL, growth factors, cytokines, and chemokines, and accretion of smooth muscle cells of various sources lead to atheroma formation; in advanced disease, the EC overlaying atheroma take up lipids, become EC-derived foam cells, and the cytotoxic ambient ultimately conducts to EC apoptosis. Understanding the mechanisms of EC dysfunction is a prerequisite for EC-targeted therapy to reduce the incidence of cardiovascular diseases.

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Novel role of the membrane-bound chemokine fractalkine in platelet activation and adhesion

Cited by 128 publications

References 48 publications

Novel uses for anti‐platelet agents as anti‐inflammatory drugs

Novel uses for anti‐platelet agents as anti‐inflammatory drugs

Immune Regulation by Microvascular Endothelial Cells: Directing Innate and Adaptive Immunity, Coagulation, and Inflammation

Implications of Early Structural-Functional Changes in the Endothelium for Vascular Disease

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