Regulatory effects of TLR2 on megakaryocytic cell function

Beaulieu, Lea M.; Lin, Elaine Y.; Morin, Kristine; Tanrıverdi, Kahraman; Freedman, Jane E.

doi:10.1182/blood-2010-09-304949

Cited by 99 publications

(92 citation statements)

References 51 publications

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“…However, little is known about platelet TLR expression during sepsis. Platelet activation can upregulate platelet TLR2, TLR4 and TLR9 expression (5,16,17), and in mice TLR2 ligands can alter megakaryocyte TLR expression (18).…”

Section: Introductionmentioning

confidence: 99%

Platelet Toll-like receptor expression and activation induced by lipopolysaccharide and sepsis

et al. 2018

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Platelets and Toll-like receptor (TLR) signalling play a role in the immune response during sepsis. Although preclinical knowledge about the role of platelet TLR signalling is increasing, data during human sepsis are less abundant. Moreover, controversy remains about the effect of the TLR4 agonist lipopolysaccharide (LPS) on platelet activation. We therefore assessed platelet TLR expression during human and murine sepsis. Moreover, we investigated the effect of TLR4 signalling on platelet activation and TLR expression. Platelets from healthy controls stimulated with LPS did not show classical platelet activation (P-selectin, CD63 and phosphatidylserine expression), potentiation of subthreshold agonist stimulation nor platelet-leukocyte complex formation. LPS stimulation however did increase maximal mitochondrial respiration in a TLR4-dependent manner. Platelet stimulation with LPS did not alter TLR expression. Platelet stimulation with thrombin receptor activating peptide increased TLR5 and TLR9, but not TLR2 or TLR4 expression. Platelets from patients with sepsis and mice with experimental sepsis showed platelet activation, but unaltered TLR expression. These results indicate that sepsis-induced platelet activation is not associated with altered platelet TLR expression and, although platelets are responsive to LPS, stimulation of platelet TLR4 does not result in classical platelet activation.

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Section: Introductionmentioning

confidence: 99%

Platelet Toll-like receptor expression and activation induced by lipopolysaccharide and sepsis

et al. 2018

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“…Stimulation of platelet TLR2 by Porphyromonas gingivalis results in increased platelet-neutrophil adhesion, 80 and stimulation of megakaryocytes through TLR2 results in the production of platelets with an increased proinflammatory gene and protein expression. 81 Other TLRs, pattern recognition receptors, and scavenger receptors also have functions in platelet activation and ADP, adenosine 59-diphosphate; CD40L, CD40 ligand; DC, dendritic cell; GPIba, glycoprotein Iba; IL, interleukin; MIP, macrophage-inflammatory protein; MMP, metalloproteinase; NAP, neutrophil-activating peptide; PDGF, platelet-derived growth factor; PF4, platelet factor 4; PMN, neutrophil; ppbp, proplatelet basic protein; SDF, stromal cell-derived factor; TGF, transforming growth factor; Th, T helper; TNF, tumor necrosis factor; VEGF, vascular endothelial growth factor; VWF, von Willebrand factor. thrombosis, including TLR9 and CD36, but their role in inflammation and platelet immune cell interactions remains to be determined.…”

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confidence: 99%

Emerging roles for platelets as immune and inflammatory cells

Morrell

Aggrey

Chapman

et al. 2014

Blood

612

514

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Despite their small size and anucleate status, platelets have diverse roles in vascular biology. Not only are platelets the cellular mediator of thrombosis, but platelets are also immune cells that initiate and accelerate many vascular inflammatory conditions. Platelets are linked to the pathogenesis of inflammatory diseases such as atherosclerosis, malaria infection, transplant rejection, and rheumatoid arthritis. In some contexts, platelet immune functions are protective, whereas in others platelets contribute to adverse inflammatory outcomes. In this review, we will discuss platelet and platelet-derived mediator interactions with the innate and acquired arms of the immune system and platelet-vessel wall interactions that drive inflammatory disease. There have been many recent publications indicating both important protective and adverse roles for platelets in infectious disease. Because of this new accumulating data, and the fact that infectious disease continues to be a leading cause of death globally, we will also focus on new and emerging concepts related to platelet immune and inflammatory functions in the context of infectious disease.

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“…50,51,56 However, MKs are distinguished from other progenitor cell types by a number of features, including the intracellular localization of HA and cognate receptors. 30,57 Despite pronounced thrombocytopenia in Hyal-2 KO animals, we found a statistically insignificant decrease in the number of MKs present within the BM when compared with controls ( Figure 1B). Our present data also reveal that maturation ( Figure 3B) and survival (Figure 2, CeE) of MKs in Hyal-2 KO animals are severely impaired.…”

Section: Discussionmentioning

confidence: 73%

“…An increasing body of literature supports the role of HA-mediated signaling through several receptors, including CD44, RHAMM, and TLR-2 and TLR-4, all of which are expressed by MKs. 30,57,62 In particular, both RHAMM and . n Z 8 WT and 12 Hyal-2 KO mice (A); n Z 12 (B).…”

Section: Hyal-2 and Efficient Thrombopoiesismentioning

confidence: 99%

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Hyaluronan Depolymerization by Megakaryocyte Hyaluronidase-2 Is Required for Thrombopoiesis

Petrey

Obery

Kessler

et al. 2016

The American Journal of Pathology

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Hyaluronan is the predominant glycosaminoglycan component of the extracellular matrix with an emerging role in hematopoiesis. Modulation of hyaluronan polymer size is responsible for its control over cellular functions, and the balance of hyaluronan synthesis and degradation determines its molecular size. Although two active somatic hyaluronidases are expressed in mammals, only deficiency in hyaluronidase-2 (Hyal-2) results in thrombocytopenia of unknown mechanism. Our results reveal that Hyal-2 knockout mice accumulate hyaluronan within their bone marrow and within megakaryocytes, the cells responsible for platelet generation. Proplatelet formation by Hyal-2 knockout megakaryocytes was disrupted because of abnormal formation of the demarcation membrane system, which was dilated and poorly developed. Importantly, peptide-mediated delivery of exogenous hyaluronidase rescued deficient proplatelet formation in murine and human megakaryocytes lacking Hyal-2. Together, our data uncover a previously unsuspected mechanism of how hyaluronan and Hyal-2 control platelet generation.

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Regulatory effects of TLR2 on megakaryocytic cell function

Cited by 99 publications

References 51 publications

Platelet Toll-like receptor expression and activation induced by lipopolysaccharide and sepsis

Platelet Toll-like receptor expression and activation induced by lipopolysaccharide and sepsis

Emerging roles for platelets as immune and inflammatory cells

Hyaluronan Depolymerization by Megakaryocyte Hyaluronidase-2 Is Required for Thrombopoiesis

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