Research Article: Crosstalk between Platelets and the Immune System: Old Systems with New Discoveries

Date Published: September 12, 2012

Publisher: Hindawi Publishing Corporation

Author(s): Conglei Li, June Li, Yan Li, Sean Lang, Issaka Yougbare, Guangheng Zhu, Pingguo Chen, Heyu Ni.

http://doi.org/10.1155/2012/384685

Abstract

Platelets are small anucleate cells circulating in the blood. It has been recognized for more than 100 years that platelet adhesion and aggregation at the site of vascular injury are critical events in hemostasis and thrombosis; however, recent studies demonstrated that, in addition to these classic roles, platelets also have important functions in inflammation and the immune response. Platelets contain many proinflammatory molecules and cytokines (e.g., P-selectin, CD40L, IL-1β, etc.), which support leukocyte trafficking, modulate immunoglobulin class switch, and germinal center formation. Platelets express several functional Toll-like receptors (TLRs), such as TLR-2, TLR-4, and TLR-9, which may potentially link innate immunity with thrombosis. Interestingly, platelets also contain multiple anti-inflammatory molecules and cytokines (e.g., transforming growth factor-β and thrombospondin-1). Emerging evidence also suggests that platelets are involved in lymphatic vessel development by directly interacting with lymphatic endothelial cells through C-type lectin-like receptor 2. Besides the active contributions of platelets to the immune system, platelets are passively targeted in several immune-mediated diseases, such as autoimmune thrombocytopenia, infection-associated thrombocytopenia, and fetal and neonatal alloimmune thrombocytopenia. These data suggest that platelets are important immune cells and may contribute to innate and adaptive immunity under both physiological and pathological conditions.

Partial Text

Platelets, which were first identified around 130 years ago, are small anucleate cells circulating in the blood with a diameter of 1-2 microns [1–5]. They are the second most abundant cells, after red blood cells, in the blood circulation with a normal concentration of 150–400 × 109/L in humans. Platelets are produced from their precursor megakaryocytes in the bone marrow [4–8]; immature larger proplatelets are initially released by megakaryocytes into the blood due to local shear stresses in the bone marrow. These proplatelets may further mature in the lung, although the process is largely unknown [8, 9].

In vertebrates, there are two types of immunity to protect the host from infection: innate and adaptive. The innate immune system is genetically programmed to detect invariant features of invading microbial pathogens, while the adaptive immune system employs antigen-specific receptors that are generated de novo in each species [54]. Phagocytosis was first described by Metchnikoff more than a century ago, but research into innate immunity was largely overshadowed by the discovery of antibodies, CD4+ and CD8+ T cells, and other components of the adaptive immune response [55]. However, the recent discovery of pathogen recognition receptors (PRRs), such as Toll-like receptors (TLRs), Nod-like receptors, and RIG-I-like receptors, which recognize pathogen-associated molecular patterns (PAMPs) that are conserved among microbial pathogens, has greatly advanced our understanding of innate immunity. Platelets express many immunomodulatory molecules (e.g., P-selectin, TLRs, CD40L) and cytokines (e.g., IL-1β, TGF-β) and have the ability to interact with various immune cells. These properties confer platelets the ability to influence both innate and adaptive immune responses [48]. Alternatively, the immune system (e.g., antibodies, cytokines, immune cells) may target platelets and lead to several immune-mediated diseases, such as autoimmune thrombocytopenia, infection-associated thrombocytopenia, and fetal and neonatal alloimmune thrombocytopenia.

Thrombocytopenia is a disorder in which the number of circulating platelets is abnormally low (<150 × 109/L). Decreased platelet counts may lead to a severe bleeding diathesis, which, in some cases, may be life-threatening [48]. There are several major categories of thrombocytopenia, grouped according to the cause of the disease: (1) immune-mediated thrombocytopenia, (2) genetic deficiency-associated thrombocytopenia, and (3) malignancy-associated thrombocytopenia, which may occur in diseases such as chronic lymphocytic leukemia and lymphomas, prostate, breast, and ovarian cancers [105–109]. It is well known that platelets play critical roles in hemostasis and thrombosis. However, exciting recent studies have revealed many new roles of platelets, such as inflammation/immune responses, tumour growth and metastasis, angiogenesis, and so forth. These new data have revolutionized our understanding of platelet functions. Platelets contain many immunologically functional molecules and contribute to both innate and adaptive immunity, which establishes platelets as immune cells. Considering their abundance in the blood, platelets may act as sentinels to identify invading microorganisms through platelet TLRs. In addition, platelets are also involved in lymphatic vessel development. In addition to the active contributions of platelets to immunity, platelets are also passively targeted in several immune-mediated diseases, although the pathogenesis is not well understood. It remains unknown whether platelets themselves contribute to the initiation or development of these platelet-targeted immune-mediated diseases. Further exploration of the interaction between platelets and the immune system may provide insights into autoimmune diseases, including the chronic process of atherosclerosis, and lead to the development of new therapies to control diseases such as infection and malignant tumors, as well as bleeding disorders.   Source: http://doi.org/10.1155/2012/384685

 

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