Platelets, inflammation and anti-inflammatory effects of antiplatelet drugs in ACS and CAD

Müller, K.; Chatterjee, Mainak; Rath, Dominik; Geisler, Tobias

doi:10.1160/th14-11-0947

Cited by 66 publications

(65 citation statements)

References 198 publications

(196 reference statements)

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“…Platelets are a major source of CXC-chemokines including CXCL4 (PF4), CXCL11 [36], CXCL12 (SDF-1), CXCL16 [33] and CCL-chemokines, such as CCL5/RANTES [37], cytokines like IL1 [38-40] or chemokine-like cytokines such as MIF [41]. Chemokines like CXCL12 or CXCL4 recruit inflammatory and regenerative endothelial cells, modulate a pro- and anti-angiogenic response, and exert antimicrobial activities [4, 42, 43].…”

Section: Discussionmentioning

confidence: 99%

Platelets as a Novel Source of Pro-Inflammatory Chemokine CXCL14

Witte¹,

Chatterjee²,

Läng³

et al. 2017

Cell Physiol Biochem

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Objective: Platelets are a major source of chemokines. Here, we demonstrate for the first time that platelets express significant amounts of CXCL14 and disclose powerful effects of platelet-derived CXCL14 on monocyte and endothelial migration. Methods: The expression of CXCL14 in platelets and in the supernatant of activated platelets was analysed by immunoblotting, ELISA, and flow cytometry. The effect of platelet-derived CXCL14 on monocyte migration was evaluated using a modified Boyden chamber. The effect of CXCL14 on monocyte phagocytosis was tested by using fluorochrome-labelled E.coli particles. The effect of platelet-derived CXCL14 on endothelial migration was explored by the use of an endothelial scratch assay. Results: Hitherto unrecognized expression of CXCL14 in human and murine platelets was uncovered by immunoblotting. Activation with platelet agonists such as adenosine-di-phosphate (ADP), collagen-related peptide (CRP), or thrombin-receptor activating peptide (TRAP), increased CXCL14 surface expression (flow cytometry) and release into the supernatant (immunoblotting, ELISA). Since CXCL14 is known to be chemotactic for CD14⁺ monocytes, we investigated the chemotactic potential of platelet-derived CXCL14 on human monocytes. Activated platelet supernatant induced monocyte migration, which was counteracted upon neutralization of platelet-derived CXCL14 as compared to IgG control. Blocking of the chemokine receptor CXCR4, but not CXCR7, reduced the number of migratory monocytes towards recombinant CXCL14, suggesting the involvement of CXCR4 in the CXCL14-directed monocyte chemotaxis. Recombinant CXCL14 enhanced the phagocytic uptake of E.coli particles by monocytes. In scratch assays with cultured endothelial cells (HUVECs), platelet-derived CXCL14 counteracted the pro-angiogenic effects of VEGF, supporting its previously recognized angiostatic potential. Conclusions: Platelets are a relevant source of CXCL14. Platelet-derived CXCL14 at the site of vascular lesions might play an important role in vascular repair/regeneration.

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Section: Discussionmentioning

confidence: 99%

Platelets as a Novel Source of Pro-Inflammatory Chemokine CXCL14

Witte¹,

Chatterjee²,

Läng³

et al. 2017

Cell Physiol Biochem

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“…Among the most potent inflammatory signaling molecules secreted by platelets are chemokines (Table I): RANTES (CCL5) binding inflamed endothelium, CXCL5, CCL3 and PF4 (CXCL4) (Raphael et al 2015). The mediators released from platelet granules, specially adhesive proteins, growth factors, chemokines important in hemostasis, may be implicated together with MMPs in the progression of inflammatory process (Morrell et al 2014) and facilitates the involvement of platelets in acute chronic inflammatory diseases (Müller et al 2015). Moreover, the expression of various and numerous membrane receptors (Table II), both constitutive and activation-dependent (P-selectin, PSGL-1, CD40, GPIb/ IX/V complex and integrin αIIbβ3) mediates platelet adhesion and aggregation involved not only in hemostasis and thrombosis, but also in inflammation (Lam et al 2015).…”

Section: Platelets Contribution In Inflammatory Processesmentioning

confidence: 99%

The physiology of blood platelets and changes of their biological activities in multiple sclerosis

Wachowicz¹,

Morel²,

Miller³

et al. 2016

Acta Neurobiologiae Experimentalis

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Increasing evidence indicates that blood platelets contribute to diverse processes that extend beyond hemostasis. Many of the same mechanisms that play a role in hemostasis and thrombosis facilitate platelets the participation in other physiological and pathological processes, particularly in the inflammation, the immune response and central nervous system disorders. Platelets are involved in pathophysiology of central nervous system diseases, especially in the pathogenesis of multiple sclerosis, but their role appears to be neglected. Platelets contribute to the inflammation and cooperate with immune cells in inflammatory and immune responses. These blood cells were identified in inflamed spinal cord and in the brain in chronic active lesions of multiple sclerosis and in the related animal models referred as Experimental Autoimmune Encephalomyelitis. This review summarizes recent insights in the platelet activation accompanied by the exocytosis of bioactive compounds stored in granules, formation of platelet microparticles, expression of specific membrane receptors, synthesis of numerous biomediators, generation of free radicals, and introduces the mechanisms by which activated platelets may be involved in the pathophysiology of multiple sclerosis. Understanding the role of platelets in multiple sclerosis may be essential for improved therapies.

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“…acetylsalicylic acid) given its primary anti-aggregatory mechanism of action. However, with the emerging evidence on role of platelets in inflammatory reactions and immunomodulation, platelet inhibition with aspirin has been found to also elicit also anti-inflammatory effects [7, 8, 9•, 10]. Moreover, aspirin was found to work as acetylating agent with a range of beneficial effects on vascular endothelium beyond platelet inhibition.…”

Section: Introductionmentioning

confidence: 99%

Effects of Aspirin on Endothelial Function and Hypertension

2016

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Purpose of reviewEndothelial dysfunction is intimately related to the development of various cardiovascular diseases, including hypertension, and is often used as a target for pharmacological treatment. The scope of this review is to assess effects of aspirin on endothelial function and their clinical implication in arterial hypertension.Recent findingsEmerging data indicate the role of platelets in the development of vascular inflammation due to the release of proinflammatory mediators, for example, triggered largely by thromboxane. Vascular inflammation further promotes oxidative stress, diminished synthesis of vasodilators, proaggregatory and procoagulant state. These changes translate into vasoconstriction, impaired circulation and thrombotic complications. Aspirin inhibits thromboxane synthesis, abolishes platelets activation and acetylates enzymes switching them to the synthesis of anti-inflammatory substances.SummaryAspirin pleiotropic effects have not been fully elucidated yet. In secondary prevention studies, the decrease in cardiovascular events with aspirin outweighs bleeding risks, but this is not the case in primary prevention settings. Ongoing trials will provide more evidence on whether to expand the use of aspirin or stay within current recommendations.

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Platelets, inflammation and anti-inflammatory effects of antiplatelet drugs in ACS and CAD

Cited by 66 publications

References 198 publications

Platelets as a Novel Source of Pro-Inflammatory Chemokine CXCL14

Platelets as a Novel Source of Pro-Inflammatory Chemokine CXCL14

The physiology of blood platelets and changes of their biological activities in multiple sclerosis

Effects of Aspirin on Endothelial Function and Hypertension

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