Anti-inflammatory effects of clopidogrel intake in renal transplant patients: Effects on platelet-leukocyte interactions, platelet CD40 ligand expression, and proinflammatory biomarkers

Graff, Jochen; Harder, Sebastian; Wahl, Oliver; Scheuermann, Ernst-Heinrich; Goßmann, Jan

doi:10.1016/j.clpt.2005.08.002

Cited by 68 publications

(43 citation statements)

References 45 publications

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“…This is relevant in relation to the potential role of platelet-derived proteins in the functional cross-talk with lymphocytes; for example, CD40 ligand translocates to the platelet membrane surface in association with the activation-induced α-granule release reaction (35). Unlike Asp, Clo has been found by different investigators to down-regulate the expression of markers of inflammation, including CD40 ligand, on the surface of activated platelets (36), an effect through which it inhibits heterotypic platelet-leukocyte interactions linking vascular injury to inflammation (37). Therefore, the beneficial effect of dual antiplatelet therapy in ameliorating the course of immune-mediated chronic hepatitis may involve distinct pharmacological effects of the two administered drugs (8).…”

Section: Discussionmentioning

confidence: 99%

Antiplatelet therapy prevents hepatocellular carcinoma and improves survival in a mouse model of chronic hepatitis B

Sitia

Aiolfi

Lucia

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

277

283

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Chronic infection with hepatitis B virus (HBV) is a major risk factor for the development of hepatocellular carcinoma (HCC). The pathogenesis of HBV-associated HCC involves both viral and host factors. The latter include a functionally inefficient CD8 + T-cell response that fails to clear the infection from the liver but sustains a chronic necroinflammatory process that contributes to the development of HCC. According to this scenario, amelioration of immune-mediated chronic liver injury may prevent HCC. Because platelets facilitate immune-mediated liver injury by promoting the hepatic accumulation of virus-specific CD8 + T cells, we evaluated the long-term consequences of antiplatelet therapy in an HBV transgenic mouse model of chronic immune-mediated necroinflammatory liver disease that progresses to HCC. Treatment with aspirin and clopidogrel during the chronic phase of the disease diminished the number of intrahepatic HBV-specific CD8 + T cells and HBV-nonspecific inflammatory cells, the severity of liver fibrosis, and the development of HCC. Antiplatelet therapy improved overall survival without causing significant side effects. In contrast, the same antiplatelet regimen had no antitumor effect when HCC was induced nonimmunologically by chronic exposure to a hepatotoxic chemical. The unprecedented observation that antiplatelet therapy inhibits or delays immune-mediated hepatocarcinogenesis suggests that platelets may be key players in the pathogenesis of HBV-associated liver cancer and supports the notion that immune-mediated necroinflammatory reactions are an important cause of hepatocellular transformation during chronic hepatitis.

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Section: Discussionmentioning

confidence: 99%

Antiplatelet therapy prevents hepatocellular carcinoma and improves survival in a mouse model of chronic hepatitis B

Sitia

Aiolfi

Lucia

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

277

283

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“…Platelet interaction with plasmacytoid dendritic cells via CD40L/CD40 potentiates IFN-α secretion in vitro , and anti-platelet therapy protects from kidney failure in lupus-prone mice. Increased platelet counts are also found in renal transplants (118) and PLAs contribute to the high cardiovascular mortality rate in renal transplant, dialysis and chronic kidney disease patients (119–121), highlighting PLAs as a potential biomarker for renal diseases and prognosis of patients.…”

Section: Platelet-leukocyte Interactions In Pathologic Conditionsmentioning

confidence: 99%

Measuring and interpreting platelet-leukocyte aggregates

et al. 2018

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Platelets, besides their specialised role in haemostasis and atherothrombosis, actively modulate innate and adaptive immune responses with crucial roles in immune surveillance, inflammation and host defence during infection. An important prerequisite for platelet-mediated changes of immune functions involves direct engagement with different types of leukocytes. Indeed, increased platelet-leukocyte aggregates (PLAs) within the circulation and/or locally at the site of inflammation represent markers of many thrombo-inflammatory diseases, such as cardiovascular diseases, acute lung injury, renal and cerebral inflammation. Therefore, measurement of PLAs could provide an attractive and easily accessible prognostic and/or diagnostic tool for many diseases. To measure PLAs in different (patho-)physiological settings in human and animal models flow cytometric and microscopic approaches have been applied. These techniques represent complementary tools to study different aspects relating to the involvement of leukocyte subtypes and molecules, as well as location of PLAs within tissues, dynamics of their interactions and/or dynamic changes in leukocyte and platelet behaviour. This review summarises various approaches to measure and interpret PLAs and discusses potential experimental factors influencing platelet binding to leukocytes. Furthermore, we summarise insights gained from studies regarding the underlying mechanism of platelet-leukocyte interactions and discuss implications of these interactions in health and disease.

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“…Indeed, clopidogrel withdrawal results in the re-emergence of inflammation in patients with diabetes and coronary artery disease (Angiolillo et al, 2006). Clopidogrel significantly reduces platelet-associated inflammatory markers in renal transplant patients with no clinical signs of atherosclerosis (Graff et al, 2005) and patients with stable coronary artery disease, for example P-selectin and CD40L release, platelet-leukocyte complexes and MMP9 release (Klinkhardt et al, 2002;Azar et al, 2006). This increased inflammatory activity of platelets in renal transplant patients may account for the high cardiovascular mortality rate as a result of the development of atherosclerotic lesions in such patients.…”

Section: Purinergic Receptor Antagonistsmentioning

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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Anti-inflammatory effects of clopidogrel intake in renal transplant patients: Effects on platelet-leukocyte interactions, platelet CD40 ligand expression, and proinflammatory biomarkers

Cited by 68 publications

References 45 publications

Antiplatelet therapy prevents hepatocellular carcinoma and improves survival in a mouse model of chronic hepatitis B

Antiplatelet therapy prevents hepatocellular carcinoma and improves survival in a mouse model of chronic hepatitis B

Measuring and interpreting platelet-leukocyte aggregates

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

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