Editorial [Hot Topic:Platelets in Inflammation and Inflammatory Disorders Guest Editor: Armen Yuri Gasparyan ]

E-ISSN： 2212-4055|9|5|319-321

ISSN： 1871-5281

Source： Inflammation & Allergy-Drug Targets (Formerly Current Drug Targets - Inflammation & Allergy), Vol.9, Iss.5, 2010-12, pp. : 319-321

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Abstract

Over the past few decades, our understanding of the molecular basis of the platelet production and function has substantially advanced. It has become clear that these anucleate cells are not just passively circulating fragments of megakaryocytes, but functionally active, autonomous agents, capable of producing a range of humoral mediators [1]. Though initially platelets were viewed as contributors to hemostasis and wound repair, advances in flow cytometry and proteomics research have identified numerous bioactive platelet proteins and broadened the scope of platelet-mediated physiological and pathological conditions [2].Platelet membrane is full of functionally active proteins, facilitating platelet adhesion, aggregation and interaction with other blood and vascular cells. Examples of the critical importance of these membranous proteins are autosomal recessive hemorrhagic disorders caused by qualitative and quantitative changes of glycoprotein (GP) IIb/IIIa in Glazmann's thrombasthenia [3, 4] and by defect of GPIb/IX/V in Bernard-Soulier syndrome [5, 6]. On the other hand, genetically determined changes of these and other platelet receptors (e.g., GPIa/IIa and GPVI) predispose to unresponsiveness to antithrombotic agents, resulting in thrombotic events [7, 8]. Additionally, platelets have been found to express proteins belonging to the Toll-like receptors family, thereby facilitating the defense of the human organism against infectious agents [9, 10].Structures inside the platelet, particularly alpha-, dense granules and lysosomes, are now well characterized. Alpha-granules are known to produce hundreds of bioactive proteins involved in the initiation and propagation of diverse thrombotic, inflammatory, immune, and metabolic disorders [11]. Some of the well-described proteins stored in and released from alphagranules are P-selectin, fibrinogen, von Willebrand factor, beta-thromboglobulin, CD40 ligand, and transforming growth factorbeta. These and many other proteins derived from alpha-granules play multiple, at times opposite roles, thus facilitating the involvement of activated platelets in a wide range of disorders.The multifaceted role of platelets and its agents has been comprehensively described within the frames of atherosclerosis, where immune, inflammatory and thrombotic pathways are intimately interrelated [12-14]. Some of the platelet agents released from alpha-granules (e.g., CD40 ligand) have been found to possess both pro-inflammatory and pro-thrombotic properties and to be independently associated with atherothrombotic events [15]. Evidence is also accumulating regarding the proinflammatory and pro-thrombotic roles of platelet-derived microparticles [16]. These microparticles are abundantly produced in conditions associated with vascular inflammation, such as acute coronary syndromes, vascular interventions, and diabetes, where the interaction of immune and inflammatory mechanisms brings about thrombosis [17]. Importantly, platelet-derived microparticles may also link inflammation with joint involvement in rheumatic diseases, particularly in rheumatoid arthritis [18]. Recently, several lines of evidence have appreciated the crucial role of activated platelets in cardiovascular involvement in rheumatoid arthritis [19] and some other autoimmune disorders [20]. A bulk of available evidence suggests that activated platelets are emerging targets of anti-inflammatory and antithrombotic therapies in rheumatic diseases [21-23]. Given the fact that functional characteristics of circulating platelets are predetermined at the stage of megakaryocytopoiesis [24], it is possible to speculate that optimal antithrombotic strategies in rheumatic and other chronic inflammatory disorders will target the megakaryocyte-platelet-microparticles axis. In this regard, the size of circulating platelets, reflecting the level of platelets production and their activity [25], may well serve as a means for monitoring antithrombotic therapies.T