Evidence map›Paper›PMID 19494325›Full record

ArticleJournal of immunology (Baltimore, Md. : 1950)2009

Lipopolysaccharide stimulates platelet secretion and potentiates platelet aggregation via TLR4/MyD88 and the cGMP-dependent protein kinase pathway.

Guoying Zhang, Jingyan Han, Emily J Welch, Richard D Ye, Tatyana A Voyno-Yasenetskaya, Asrar B Malik, Xiaoping Du, Zhenyu Li

Open access · bronzeAbstract read
In one paragraph

Article in Journal of immunology (Baltimore, Md. : 1950), 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 191 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
191citing papers in PubMed, 3 pooled it
7.2field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

191 citing papers in PubMed, 3 syntheses or guidelines pooled it, 356 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Review
  5. Activation of TLR4 promotes oxidative inflammation via NADPH oxidase signaling in platelets of subjects with autism spectrum disorder.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2026
    Article
  6. Review
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  9. Article
  10. Induced pluripotent stem cell-derived platelets kill multidrug-resistantResearch and practice in thrombosis and haemostasis · 2026
    Article
  11. Review
  12. Platelet lipidome alterations in septic shock: a matched case-control study.Research and practice in thrombosis and haemostasis · 2026
    Article
  13. Review
  14. Article
  15. Article
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  18. Article
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131 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 1 country.

Guoying ZhangDepartment of Pharmacology, University of Illinois, Chicago, IL 60612, USA.
Jingyan Han
Emily J Welch
Richard D Ye
Tatyana A Voyno-Yasenetskaya
Asrar B Malik
Xiaoping Du
Zhenyu Li
University of Kentucky · USIllinois College · US

Funding

THROMBOSPONDIN1 MEDIATES MACROPHAGE INFILTRATION INTO ADIPOSE TISSUE AND PROMOTEP20RR021954 · NCRR · UNIVERSITY OF KENTUCKY · PI CASSIS, LISA A · 2008 to 2011
$8.3M
Signaling mechanisms of platelet GPIb-IXR01HL062350 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI DU, XIAOPING · 2000 to 2017
$6.0M
Outside-in signaling mechanisms of platelet integrin alpha-llb-beta3R01HL080264 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI DU, XIAOPING · 2007 to 2019
$4.6M
The roles of protein kinase G in platelet activationR01HL068819 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI DU, XIAOPING · 2002 to 2009
$2.8M
NCRR NIH HHS P20 RR021954NCRR NIH HHS P20RR021954-01A1NHLBI NIH HHS HL62350NHLBI NIH HHS HL68819NHLBI NIH HHS R01 HL062350NHLBI NIH HHS R01 HL068819NHLBI NIH HHS R01 HL080264PHS HHS 080264
6 · The paper itself

Abstract

Bacterial LPS induces rapid thrombocytopenia, hypotension, and sepsis. Although growing evidence suggests that platelet activation plays a critical role in LPS-induced thrombocytopenia and tissue damage, the mechanism of LPS-mediated platelet activation is unclear. In this study, we show that LPS stimulates platelet secretion of dense and alpha granules as indicated by ATP release and P-selectin expression, and thus enhances platelet activation induced by low concentrations of platelet agonists. Platelets express components of the LPS receptor-signaling complex, including TLR (TLR4), CD14, MD2, and MyD88, and the effect of LPS on platelet activation was abolished by an anti-TLR4-blocking Ab or TLR4 knockout, suggesting that the effect of LPS on platelet aggregation requires the TLR4 pathway. Furthermore, LPS-potentiated thrombin- and collagen-induced platelet aggregation and FeCl(3)-induced thrombus formation were abolished in MyD88 knockout mice. LPS also induced cGMP elevation and the stimulatory effect of LPS on platelet aggregation was abolished by inhibitors of NO synthase and the cGMP-dependent protein kinase (PKG). LPS-induced cGMP elevation was inhibited by an anti-TLR4 Ab or by TLR4 deficiency, suggesting that activation of the cGMP/protein kinase G pathway by LPS involves the TLR4 pathway. Taken together, our data indicate that LPS stimulates platelet secretion and potentiates platelet aggregation through a TLR4/MyD88- and cGMP/PKG-dependent pathway.

Indexed as

AnimalsBlood PlateletsCyclic GMPCyclic GMP-Dependent Protein KinasesHumansLipopolysaccharide ReceptorsLipopolysaccharidesLymphocyte Antigen 96MiceMyeloid Differentiation Factor 88Platelet AggregationProtein BindingSignal TransductionThrombinToll-Like Receptor 4Cyclic GMPCyclic GMP-Dependent Protein KinasesLipopolysaccharide ReceptorsLipopolysaccharidesLY96 protein, humanLymphocyte Antigen 96Myeloid Differentiation Factor 88ThrombinToll-Like Receptor 4

Identifiers

PMID19494325
PMCPMC2787095
OpenAlexW1554780345

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.