Non-Hemostatic Functions of Human Blood Platelets: Effects of Bioactive Compounds (original) (raw)

Beyond Hemostasis: The Role of Platelets in Inflammation, Malignancy and Infection

Cardiovascular & Haematological Disorders - Drug Targets(formerly Current Drug Targets - Cardiovascular & Hematological Disorders), 2008

Platelets play a complex role in hemostasis and thrombosis. The expression of multiple membrane receptors, both constitutive and activation-dependent, mediates platelet adhesion and aggregation at sites of vascular lesion. Platelet activation leads to exocytosis of granular constituents, release of newly synthesized mediators, and discharge of membrane-bound transcellular signaling molecules. Many of the same mechanisms that play a role in hemostasis and thrombosis facilitate platelet participation in other physiological or pathological processes including inflammation, malignancy and the immune response. Platelet receptors such as GPIb/IX/V, P-selectin, P-selectin glycoprotein ligand 1, CD40 and the IIbß3 integrin, crucial to hemostasis, have been implicated in the progression of such inflammatory conditions as atherosclerosis, rheumatoid arthritis and inflammatory bowel disease, in the progression and metastatic spread of malignancies, and in the immune response to bacterial challenge. The release of platelet granular contents, including adhesive proteins, growth factors and chemokines/cytokines, that serve to facilitate hemostasis and wound repair, also function in acute and chronic inflammatory disease and in tumor cell activation and growth. Platelets contribute to host defence as they recognise bacteria, recruit traditional immune cells to the site of infection and secrete bactericidal mediators. The primary focus of this review is the "non-haemostatic" functions of platelets in physiological and pathological states.

Role of Platelets in Inflammation and Cancer: Novel Therapeutic Strategies

Basic & Clinical Pharmacology & Toxicology, 2014

Platelets play a central role in inflammation through their direct interaction with other cell types, such as leucocytes and endothelial cells, and by the release of many factors, that is, lipids [such as thromboxane (TX)A 2 ] and proteins (a wide number of angiogenic and growth factors) stored in a-granules, and adenosine diphosphate (ADP), stored in dense granules. These platelet actions trigger autocrine and paracrine activation processes that lead to leucocyte recruitment into different tissues and phenotypic changes in stromal cells which contribute to the development of different disease states, such as atherosclerosis and atherothrombosis, intestinal inflammation and cancer. The signals induced by platelets may cause pro-inflammatory and malignant phenotypes in other cells through the persistent induction of aberrant expression of cyclooxygenase (COX)-2 and increased generation of prostanoids, mainly prostaglandin (PG)E 2 . In addition to cardiovascular disease, enhanced platelet activation has been detected in inflammatory disease and intestinal tumourigenesis. Moreover, the results of clinical studies have shown that the antiplatelet drug aspirin reduces the incidence of vascular events and colorectal cancer. All these pieces of evidence support the notion that colorectal cancer and atherothrombosis may share a common mechanism of disease, that is, platelet activation in response to epithelial (in tumourigenesis) and endothelial (in tumourigenesis and atherothrombosis) injury. Extensive translational medicine research is necessary to obtain a definitive mechanistic demonstration of the platelet-mediated hypothesis of colon tumourigenesis. The results of these studies will be fundamental to support the clinical decision to recommend the use of lowdose aspirin, and possibly other antiplatelet agents, in primary prevention, that is, even for individuals at low cardiovascular risk.

Platelets: Physiology and Biochemistry

Seminars in Thrombosis and Hemostasis, 2005

Platelets are specialized blood cells that play central roles in physiologic and pathologic processes of hemostasis, inflammation, tumor metastasis, wound healing, and host defense. Activation of platelets is crucial for platelet function that includes a complex interplay of adhesion and signaling molecules. This article gives an overview of the activation processes involved in primary and secondary hemostasis, for example, platelet adhesion, platelet secretion, platelet aggregation, microvesicle formation, and clot retraction/stabilization. In addition, activated platelets are predominantly involved in cross talk to other blood and vascular cells. Stimulated ''sticky'' platelets enable recruitment of leukocytes at sites of vascular injury under high shear conditions. Platelet-derived microparticles as well as soluble adhesion molecules, sP-selectin and sCD40L, shed from the surface of activated platelets, are capable of activating, in turn, leukocytes and endothelial cells. This article focuses further on the new view of receptor-mediated thrombin generation of human platelets, necessary for the formation of a stable platelet-fibrin clot during secondary hemostasis. Finally, special emphasis is placed on important stimulatory and inhibitory signaling pathways that modulate platelet function.

Platelets, thrombosis and inflammation: Recent data from pharmacological studies

2000

Platelet adhesion as well as platelet recruitment and aggregation are implicated in thrombus formation. In platelets, thromboxane A 2 is the main product of arachidonic acid via the enzyme cyclooxygenase-1 (COX-1), whose inhibition has been a target for the pharmacological inactivation of platelets. However, variability in platelet inhibition by aspirin, a COX-1 inhibitor, suggests that alternative mechanisms occur associated with platelet activation. The search for new drugs to obtain an effective platelet inhibition has provided new insights into the role of platelets in cardiovascular disease. In addition, it has favoured the development of alternative agents targeting platelets, such as ADP receptor inhibitors (e.g., clopidogrel) and blockers of the GPIIb/IIIa receptors. Recent studies have associated thrombosis and inflammation. It has been suggested that activated platelets may act as enhancers of the inflammatory reactions and, therefore, the anti-inflammatory effects associated with the anti-platelet therapy may contribute in part to the clinical beneficial effects of various drugs in clinical trials. A better knowledge of the proteins and molecular pathways involved in the regulation of platelet activation will surely help identify new possible targets to develop more efficient anti-platelet drugs in the future.

Overview of Platelet Physiology: Its Hemostatic and Nonhemostatic Role in Disease Pathogenesis

Platelets are small anucleate cell fragments that circulate in blood playing crucial role in managing vascular integrity and regulating hemostasis. Platelets are also involved in the fundamental biological process of chronic inflammation associated with disease pathology. Platelet indices like mean platelets volume (MPV), platelets distributed width (PDW), and platelet crit (PCT) are useful as cheap noninvasive biomarkers for assessing the diseased states. Dynamic platelets bear distinct morphology, where and dense granule are actively involved in secretion of molecules like GPIIb , IIIa, fibrinogen, vWf, catecholamines, serotonin, calcium, ATP, ADP, and so forth, which are involved in aggregation. Differential expressions of surface receptors like CD36, CD41, CD61 and so forth have also been quantitated in several diseases. Platelet clinical research faces challenges due to the vulnerable nature of platelet structure functions and lack of accurate assay techniques. But recent advancement in flow cytometry inputs huge progress in the field of platelets study. Platelets activation and dysfunction have been implicated in diabetes, renal diseases, tumorigenesis, Alzheimer's, and CVD. In conclusion, this paper elucidates that platelets are not that innocent as they keep showing and thus numerous novel platelet biomarkers are upcoming very soon in the field of clinical research which can be important for predicting and diagnosing disease state.

Current viewpoints on platelet contribution to inflammation

Inflammation is an underlying feature of a variety of human diseases. Because inflammatory diseases are a major cause of morbidity and mortality in developed countries, understanding the interaction of the most important factors involved is an important challenge. Although platelets are widely recognized as having a critical role in primary hemostasis and thrombosis, basic and clinical evidence increasingly identifies these enucleated cells as relevant modulators, as both effector and target cells, of the inflammatory response. The cross-talk between platelets, endothelial cells and leukocytes in the inflammatory milieu mat be seen as a double-edged sword which functions not only as an effective first-line defense mechanism but may also lead to organ failure and death in the absence of counter-regulation systems. The molecular mechanisms involved in the reciprocal activation of platelets, endothelial cells and leukocytes are beginning to be elucidated. In the light of the existing d...

The prowess of platelets in immunity and inflammation

Thrombosis and Haemostasis

SummaryPlatelets not only serve as essential haemostatic cells, they also have important roles in immune defence and inflammation. Despite not having a nucleus, platelets contain physiologically relevant amounts of RNA, which can be spliced and translated into functional proteins. In addition, platelets have the ability to bind to numerous other cells, such as leukocytes and vascular cells. During those interactions, platelets can modulate cellular responses, resulting in e. g. inflammatory activation or apoptosis. Recent studies have demonstrated that platelets can influence the outcomes of bacterial and viral infection, as well as the extent of tissue injury after ischaemia. Platelets also carry considerable amounts of cytokines and growth factors in their secretory granules, preformed for rapid secretion. Those properties in combination with the sheer amount of platelets circulating in the blood stream make them an important force in the immune response during health and disease....

Platelets: still a therapeutical target for haemostatic disorders

International journal of molecular sciences, 2014

Platelets are cytoplasmatic fragments from bone marrow megakaryocytes present in blood. In this work, we review the basis of platelet mechanisms, their participation in syndromes and in arterial thrombosis, and their potential as a target for designing new antithrombotic agents. The option of new biotechnological sources is also explored.

Role of platelets in inflammation

Dicle Medical Journal / Dicle Tip Dergisi, 2012

İnflamasyon patolojik etkenlere karşı canlı dokular tarafından oluşturulan, patojeni uzaklaştırmaya yarayan ve iyileşme sürecini başlatan son derece önemli bir olaydır. Mikroorganizmalar, fiziksel ve kimyasal travmalar, termal yaralanma, iskemi ve immün reaksiyonlar inflamasyon nedeni olarak gösterilebilir. Plateletler, nükleusa sahip olmayan ve kemik iliğinde megakaryositlerden üretilen hücreler olup kanamanın durdurulması ve hemostazın devamında rol almasının yanısıra inflamasyonda da önemli rol almaktadır. Nötrofil ve makrofajlara benzer şekilde, inflamasyon mekanizmasına etki edecek çeşitli sitokin üretimi ve salınımı yaparlar. Bu derlemede inflamasyonda plateletlerin rolleri ve inflamasyonun plateletler üzerine etkileri tartışılacaktır.