Regulation of platelet responses triggered by Toll-like receptor 2 and 4 ligands is another non-genomic role of nuclear factor-kappaB

Rivadeneyra, Leonardo; Carestia, Agostina; Etulain, Julia; Pozner, Raúl; Fondevila, Carlos; Negrotto, Soledad; Schattner, Mirta

doi:10.1016/j.thromres.2013.11.028

Cited by 82 publications

(130 citation statements)

References 44 publications

(85 reference statements)

Supporting

Mentioning

115

Contrasting

Unclassified

Order By: Relevance

“…Platelets are known to express various TLRs,5 and TLR stimulation can mediate a number of thrombotic7, 8, 21 and inflammatory processes 9, 10. Platelets and leucocytes aggregate in response to TLR stimulation,9, 12 and platelets contribute to vascular inflammation via this interaction with leucocytes.…”

Section: Discussionmentioning

confidence: 99%

Platelets regulate leucocyte responses to Toll‐like receptor stimulation

et al. 2018

View full text Add to dashboard Cite

ObjectivesPlatelets are important regulators of vascular thrombosis and inflammation and are known to express Toll‐like receptors (TLRs). Through TLRs, platelets mediate a number of responses by interacting with leucocytes. Here, we report the extent to which platelets modulate in vitro peripheral blood mononuclear cells (PBMCs) and granulocyte responses to TLR4, TLR2/1 and TLR2/6 stimulation in healthy subjects.MethodsPeripheral blood mononuclear cells and granulocytes from 10 healthy volunteers were cultured alone or cocultured with platelets. Cultures were left unstimulated or stimulated with 1 or 100 ng mL−1 of either LPS (TLR4 agonist), Pam3CSK4 (TLR2/1 agonist) or fibroblast‐stimulating lipopeptide (FSL)‐1 (TLR2/6 agonist). Neutrophil activation (CD66b expression), monocyte activation (HLA‐DR), granulocyte elastase production and PBMC cytokine and chemokine production were examined.ResultsPlatelet coculture decreased neutrophil CD66b expression in response to LPS, Pam3CSK4 and FSL‐1, and modestly decreased monocyte HLA‐DR expression in response to low‐dose LPS. Platelets reduced granulocyte elastase secretion in response to low doses of all TLR agonists tested. In response to LPS, platelet coculture reduced IL‐6, tumor necrosis factor (TNF)‐α and MIP‐1β production, and increased IL‐10 production by PBMCs. In response to FSL‐1, platelets increased IL‐6, IL‐10 and MIP‐1β production, but reduced TNF‐α production. Platelet coculture did not alter PBMC cytokine/chemokine production in response to Pam3CSK4.ConclusionThis study challenges the notion that platelets act solely in a pro‐inflammatory manner. Rather, platelets are complex immunomodulators that regulate leucocyte responses to TLR stimulation in a TLR agonist‐specific manner. Platelets may modulate leucocyte responses to dampen inflammation, and this platelet effect may play an important role in reducing inflammation‐mediated host damage.

show abstract

Section: Discussionmentioning

confidence: 99%

Platelets regulate leucocyte responses to Toll‐like receptor stimulation

et al. 2018

View full text Add to dashboard Cite

show abstract

“…35 Immunoblotting experiments showed significantly increased levels of phospho-IKK and phospho-NF-kB in low-dose thrombin-stimulated WT platelets in the presence of cFn compared with pFn ( Figure 4C). These differences were not seen in TLR4…”

Section: Cellular Fn-eda1 Potentiates Platelet Aggregation Through Tlr4mentioning

confidence: 96%

“…33 Platelet TLR4 has been shown to mediate microvascular thrombosis in endotoxemia 23 and enhanced platelet aggregation with LPS 34,35 and extracellular histones. 21 We therefore determined if the prothrombotic effect of cellular Fn-EDA1 is mediated through platelet TLR4.…”

Section: Cellular Fn-eda1 Potentiates Platelet Aggregation Through Tlr4mentioning

confidence: 99%

“…Previously, it was shown that LPS alone up to 100 mg/mL does not induce platelet aggregation. 34,35 However, LPS has been shown to potentiate platelet responses to subthreshold concentrations of agonists. 34, 35 Hence, we examined the effects of cFn on For personal use only.…”

Section: Cellular Fn-eda1 Potentiates Platelet Aggregation Through Tlr4mentioning

confidence: 99%

“…34,35 However, LPS has been shown to potentiate platelet responses to subthreshold concentrations of agonists. 34, 35 Hence, we examined the effects of cFn on For personal use only. on June 7, 2019. by guest www.bloodjournal.org From aggregation of washed platelets induced by low-dose thrombin (0.02 U/mL).…”

Section: Cellular Fn-eda1 Potentiates Platelet Aggregation Through Tlr4mentioning

confidence: 99%

See 2 more Smart Citations

Cellular fibronectin containing extra domain A promotes arterial thrombosis in mice through platelet Toll-like receptor 4

Prakash

Kulkarni

Lentz

et al. 2015

Blood

View full text Add to dashboard Cite

show abstract

Platelet TLR4 at the crossroads of thrombosis and the innate immune response

Schattner

2018

Journal of Leukocyte Biology

Self Cite

View full text Add to dashboard Cite

Platelet TLR‐4 activation by pathogen‐ or damage‐associated molecular pattern molecules triggers pro‐thrombotic, proinflammatory, and pro‐coagulant effector responses. Moreover, platelet TLR4 has a prominent role as a sensor of high lipopolysaccharide circulating levels during sepsis and in the clearance of pathogens mediated by neutrophils. This review presents evidence pointing to TLR4 as a bridge connecting thrombosis and innate immunity.

show abstract

Regulation of platelet responses triggered by Toll-like receptor 2 and 4 ligands is another non-genomic role of nuclear factor-kappaB

Cited by 82 publications

References 44 publications

Platelets regulate leucocyte responses to Toll‐like receptor stimulation

Platelets regulate leucocyte responses to Toll‐like receptor stimulation

Cellular fibronectin containing extra domain A promotes arterial thrombosis in mice through platelet Toll-like receptor 4

Platelet TLR4 at the crossroads of thrombosis and the innate immune response

Contact Info

Product

Resources

About