Pharmacological Modulation of the Inflammatory Actions of Platelets
Patients with inflammatory diseases often exhibit a change in platelet function, with these alterations being clearly distinct from the well-characterized role of platelets in haemostasis and thrombosis. It has recently been revealed that platelets can be
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Contents 1 A Dichotomy in Platelet Function . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 How Do Platelets Contribute to Inflammatory Disorders? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 Purinergic Receptor Modulation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 Modulation of Platelet Adhesion Molecules . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 NF-kB and Its Role in Platelet Activation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 Oral Glycoprotein IIb–IIIa Antagonists: Pro-inflammatory? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 Phosphodiesterase Inhibitors as an Anti-platelet Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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Abstract Patients with inflammatory diseases often exhibit a change in platelet function, with these alterations being clearly distinct from the well-characterized role of platelets in haemostasis and thrombosis. It has recently been revealed that platelets can behave as innate inflammatory cells in immune responses with roles in leukocyte recruitment, migration into tissues, release of cytotoxic mediators, and in tissue remodelling following injury. Platelets exhibit a wide range of receptors for mediators involved in the inflammatory pathway and the immune response (Fig. 1). These include purinergic receptors, selectins, integrins, toll-like receptors, immunoglobulins, and chemokine receptors, but the precise role platelets play in the inflammatory process is still under investigation. Nevertheless, given that many of these receptors are distinct from those involved in thrombosis and haemostasis, this raises the real possibility of targeting these receptors to regulate inflammatory diseases without compromising haemostasis.
R. Amison • C. Page (*) • S. Pitchford Sackler Institute of Pulmonary Pharmacology, King’s College London, 150 Stamford Street, Room 5.44, 5th Floor, Franklin-Wilkins Building, Waterloo Campus, London SE1 9NH, UK e-mail: [email protected] P. Gresele et al. (eds.), Antiplatelet Agents, Handbook of Experimental Pharmacology 210, DOI 10.1007/978-3-642-29423-5_18, # Springer-Verlag Berlin Heidelberg 2012
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Fig. 1 Dichotomy of platelet function. It is possible for platelets to become activated by either pro-thrombotic or pro-inflammatory mediators depending on the activating stimuli. Therefore, the final function of platelets is dependent o
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