The role of inflammation in regulating platelet production and function: Toll-like receptors in platelets and megakaryocytes

Abstract

Platelets have been extensively studied as hemostatic regulators, stopping uncontrolled flow of blood from an injured vessel and allowing for repair. However, multiple studies have shown that platelets can interact with bacterial proteins, particularly seen during sepsis and inflammation. Immune cells recognize pathogens through Toll-like Receptors (TLRs). These same receptors allow platelets to recognize bacterial proteins and regulate platelet immunity and function. This review examines the TLRs expressed on platelets and megakaryocytes and how these receptors affect the function of these cells. Through TLRs, platelets go beyond hemostatic regulation and play a pivotal role in inflammation and infection.

Novel phosphatidylethanolamine derivatives accumulate in circulation in hyperlipidemic ApoE−/− mice and activate platelets via TLR2

“…8,12,13,[19][20][21] The TLR2 blocking antibody strongly inhibited platelet response to CAP-PEs, whereas nonimmune isotype matched IgG (Figure 2A; supplemental Figure 5A) and TLR3-, TLR4-, and TLR9-specific blocking antibodies had no effect (supplemental Figure 5D-F). TLR2 functions as a heterodimer either with TLR1 or TLR6.…”

Platelet Ca2+ responses coupled to glycoprotein VI and Toll-like receptors persist in the presence of endothelial-derived inhibitors: roles for secondary activation of P2X1 receptors and release from intracellular Ca2+ stores

“…In addition to collagen, thrombin, and TxA 2 , we assessed responses to stimulation of Toll-like receptors (TLRs) that play important roles in innate immune responses to invading pathogens. 18 Platelets express multiple TLR receptors, 19,20 with the TLR 2/1 complex representing the major functional subtype. [21][22][23][24] These receptors may therefore contribute to the emerging roles of platelets in immune responses and thus also the development of atherosclerosis.…”

Megakaryocyte TLR2: immunity bullet?

“…7 It has been reported that TPO levels and platelet counts increase after 24 hours of exposure to low-grade endotoxemia 8 ; a possible pathway could be related to TLR2 activation. 7 Previous studies have shown megakaryocyte expression of TLRs, in particular, 1, 2, 4 and 6. 1 The purpose of these receptors and the role of inflammation on megakaryocyte maturation and platelet development is still a matter of debate to which the study by Beaulieu and colleagues significantly contributes.…”

“…Stimulation of the immune TLR2 on the platelet surface activates phosphoinositide-3-kinase (PI3K) and causes platelet activation and platelet-dependent thrombosis. 7 Inflammatory conditions are known to increase thrombopoietin (TPO) levels, thereby increasing the number of circulating platelets. 7 It has been reported that TPO levels and platelet counts increase after 24 hours of exposure to low-grade endotoxemia 8 ; a possible pathway could be related to TLR2 activation.…”

“…7 Inflammatory conditions are known to increase thrombopoietin (TPO) levels, thereby increasing the number of circulating platelets. 7 It has been reported that TPO levels and platelet counts increase after 24 hours of exposure to low-grade endotoxemia 8 ; a possible pathway could be related to TLR2 activation. 7 Previous studies have shown megakaryocyte expression of TLRs, in particular, 1, 2, 4 and 6.…”