Platelet microparticles inhibit IL-17 production by regulatory T cells through P-selectin

Dinkla, Sip; Cranenbroek, Bram van; Heijden, Wouter A van der; He, Xiaotian; Wallbrecher, Rike; Dumitriu, Ingrid E.; Ven, André J. van der; Bosman, G.J.C.G.M.; Koenen, Hans J. P. M.; Joosten, Irma

doi:10.1182/blood-2015-04-640300

Cited by 110 publications

(109 citation statements)

References 57 publications

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“…In addition to their well described PS-related procoagulant activity 49 , platelet microparticles have been shown to be predominantly found in the circulation during sepsis 50 , to have an inflammatory role in rheumatoid arthritis 51 and also to have immunosuppressive properties 52, 53 . Therefore, their contribution to the inflammatory/immunosuppressive component of sepsis should not be underestimated.…”

Section: Discussionmentioning

confidence: 99%

Acetylsalicylic acid differentially limits the activation and expression of cell death markers in human platelets exposed to Staphylococcus aureus strains

Chabert

Damien

Verhoeven

et al. 2017

Sci Rep

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Beyond their hemostatic functions, platelets alter their inflammatory response according to the bacterial stimulus. Staphylococcus aureus is associated with exacerbated inflammation and thrombocytopenia, which is associated with poor prognosis during sepsis. Acetylsalicylic acid and statins prevent platelet aggregation and decrease the mortality rate during sepsis. Therefore, we assessed whether these two molecules could reduce in vitro platelet activation and the inflammatory response to S. aureus. Platelets were exposed to clinical strains of S. aureus in the presence or absence of acetylsalicylic acid or fluvastatin. Platelet activation, aggregation, and release of soluble sCD62P, sCD40 Ligand, RANTES and GROα were assessed. Platelet cell death was evaluated by analyzing the mitochondrial membrane potential, phosphatidylserine exposure, platelet microparticle release and caspase-3 activation. All S. aureus strains induced platelet activation but not aggregation and decreased the platelet count, the expression of cell death markers and the release of RANTES and GROα. Acetylsalicylic acid but not fluvastatin limited platelet activation and inflammatory factor release and restored the platelet count by protecting platelets from Staphylococcus-induced expression of cell death markers. This study demonstrates that acetylsalicylic acid limits S. aureus-induced effects on platelets by reducing cell death, revealing new strategies to reduce the platelet contribution to bacteremia-associated inflammation.

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Section: Discussionmentioning

confidence: 99%

Acetylsalicylic acid differentially limits the activation and expression of cell death markers in human platelets exposed to Staphylococcus aureus strains

Chabert

Damien

Verhoeven

et al. 2017

Sci Rep

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“…Platelet P-selectin expression is reduced by thienopyridine class inhibitors of the adenosine pyrophosphate receptor [79]. This is relevant because platelet-derived microparticles reduce the plasticity of FOXP3(+) regulatory T cells by interacting with their P-selectin(+) subset, creating a pro-inflammatory milieu [80]. …”

Section: Discussionmentioning

confidence: 99%

Increased Soluble VCAM-1 and Normal P-Selectin in Cystic Fibrosis: a Cross-Sectional Study

Nowak

Wojsyk‐Banaszak

Mądry

et al. 2017

Lung

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PurposeAs life expectancy in cystic fibrosis (CF) increases, questions regarding its potential impact on cardiovascular health arise. Soluble vascular cell adhesion molecule 1 (sVCAM-1), P-selectin (sP-selectin) are proposed as biomarkers of cardiovascular disease. We aimed to: compare their concentrations in clinically stable CF patients and healthy subjects (HS) and verify whether they independently correlate with CF characteristics.MethodsSerum sVCAM-1 and sP-selectin levels were measured using ELISA. CF was characterized using: forced expiratory volume in 1 s, exocrine pancreatic and CF-related liver disease status, Pseudomonas aeruginosa colonization, serum high-sensitivity C-reactive protein, and body mass index (BMI). CFTR genotypes were classified as severe (classes I and II) or other.Results108 CF patients and 51 healthy subjects volunteered for the study. In the CF group BMI was lower (median [IQR]: 20.5 kg/m2 [18.4–22.2] vs. 21.6 kg/m2 [19.9–23.4], p = 0.02) and hsCRP levels were higher (3.6 mg/L [1.1–7.1] vs. 0.5 mg/dL [0.3–1.0], p < 10−10). While sVCAM-1 concentrations were greater in CF patients (1018 ng/mL [851–1279] vs. 861 ng/mL [806–979], p < 10−4), sP-selectin levels did not differ (155 ng/mL [129–188] vs. 156 ng/mL [144–177], p = 0.48). None of the multivariable regression models was valid for the prediction of sVCAM-1 and sP-selectin in CF.ConclusionsWe found higher sVCAM-1 concentrations in CF patients than in healthy subjects, which were not explained by CF characteristics. Further research is required to check whether sVCAM-1 is a marker of microangiopathy in CF.

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“…Platelets could control an IL‐17‐dependent inflammatory response. Platelet microparticles have been shown to inhibit IL‐17 through P‐selectin . Platelet factor 4 (PF4) also has been reported to inhibit IL‐17 production by suppressing cytokine signalling protein 3 .…”

Section: Discussionmentioning

confidence: 99%

Mean platelet volume as a marker for differentiating disease flare from infection in Behçet's disease

et al. 2016

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Platelet microparticles inhibit IL-17 production by regulatory T cells through P-selectin

Abstract: Key Points Platelet-derived microparticles inhibit IL-17 and IFN-γ production by Tregs and stimulate Treg stability in an inflammatory environment. Platelet-derived microparticles inhibit Treg plasticity in a P-selectin– and partially CXCR3-dependent manner.

Cited by 110 publications

References 57 publications

Acetylsalicylic acid differentially limits the activation and expression of cell death markers in human platelets exposed to Staphylococcus aureus strains

Acetylsalicylic acid differentially limits the activation and expression of cell death markers in human platelets exposed to Staphylococcus aureus strains

Increased Soluble VCAM-1 and Normal P-Selectin in Cystic Fibrosis: a Cross-Sectional Study

Mean platelet volume as a marker for differentiating disease flare from infection in Behçet's disease

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