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Increased platelet reactivity in idiopathic pulmonary fibrosis is mediated by a plasma factor.

Crooks MG, Fahim A, Naseem KM, Morice AH, Hart SP - PLoS ONE (2014)

Bottom Line: Platelet P-selectin expression was significantly greater in IPF patients than controls following stimulation with 0.1 µM ADP (1.9% positive ±0.5 (mean ± SEM) versus 0.7%±0.1; p = 0.03), 1 µM ADP (9.8%±1.3 versus 3.3%±0.8; p<0.01) and 10 µM ADP (41.3%±4.2 versus 22.5%±2.6; p<0.01).Re-suspension of control platelets in plasma taken from subjects with IPF resulted in increased platelet activation compared to control plasma.IPF patients exhibit increased platelet reactivity compared with controls.

View Article: PubMed Central - PubMed

Affiliation: Centre for Cardiovascular and Metabolic Research, Hull York Medical School, Cottingham, United Kingdom.

ABSTRACT

Introduction: Idiopathic Pulmonary Fibrosis (IPF) is a progressive, incurable fibrotic interstitial lung disease with a prognosis worse than many cancers. Its pathogenesis is poorly understood. Activated platelets can release pro-fibrotic mediators that have the potential to contribute to lung fibrosis. We determine platelet reactivity in subjects with IPF compared to age-matched controls.

Methods: Whole blood flow cytometry was used to measure platelet-monocyte aggregate formation, platelet P-selectin expression and platelet fibrinogen binding at basal levels and following stimulation with platelet agonists. A plasma swap approach was used to assess the effect of IPF plasma on control platelets.

Results: Subjects with IPF showed greater platelet reactivity than controls. Platelet P-selectin expression was significantly greater in IPF patients than controls following stimulation with 0.1 µM ADP (1.9% positive ±0.5 (mean ± SEM) versus 0.7%±0.1; p = 0.03), 1 µM ADP (9.8%±1.3 versus 3.3%±0.8; p<0.01) and 10 µM ADP (41.3%±4.2 versus 22.5%±2.6; p<0.01). Platelet fibrinogen binding was also increased, and platelet activation resulted in increased platelet-monocyte aggregate formation in IPF patients. Re-suspension of control platelets in plasma taken from subjects with IPF resulted in increased platelet activation compared to control plasma.

Conclusions: IPF patients exhibit increased platelet reactivity compared with controls. This hyperactivity may result from the plasma environment since control platelets exhibit increased activation when exposed to IPF plasma.

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Related in: MedlinePlus

Platelet fibrinogen binding in IPF patients and controls.A. Representative flow cytometry histogram demonstrating platelet fibrinogen binding under basal (unstimulated) conditions. B. Flow cytometry histogram demonstrating platelet fibrinogen binding following stimulation with 10 µM ADP. C. Percentage of platelets binding fibrinogen at basal levels and in response to the platelet agonists ADP (0.1–10 µM) or TFLLR (1–10 µM). * P≤0.01.
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pone-0111347-g004: Platelet fibrinogen binding in IPF patients and controls.A. Representative flow cytometry histogram demonstrating platelet fibrinogen binding under basal (unstimulated) conditions. B. Flow cytometry histogram demonstrating platelet fibrinogen binding following stimulation with 10 µM ADP. C. Percentage of platelets binding fibrinogen at basal levels and in response to the platelet agonists ADP (0.1–10 µM) or TFLLR (1–10 µM). * P≤0.01.

Mentions: The percentage of platelets binding fibrinogen was significantly higher in IPF patients compared with controls following stimulation with 0.1 µM and 1 µM ADP (0.1 µM ADP: 50.3%±8.9 versus 17.5%±6.1; p = <0.01; 1 µM ADP: 77.9%±4.6 versus 56.2%±6.5; p = <0.01). There was no significant difference in fibrinogen binding under basal (unstimulated) conditions (19.9%±6.0 versus 8.7%±3.2 respectively; p = 0.13). The increase in fibrinogen binding in IPF subjects following stimulation with TFLLR did not reach statistical significance (figure 4 and table S5 in file S1).


Increased platelet reactivity in idiopathic pulmonary fibrosis is mediated by a plasma factor.

Crooks MG, Fahim A, Naseem KM, Morice AH, Hart SP - PLoS ONE (2014)

Platelet fibrinogen binding in IPF patients and controls.A. Representative flow cytometry histogram demonstrating platelet fibrinogen binding under basal (unstimulated) conditions. B. Flow cytometry histogram demonstrating platelet fibrinogen binding following stimulation with 10 µM ADP. C. Percentage of platelets binding fibrinogen at basal levels and in response to the platelet agonists ADP (0.1–10 µM) or TFLLR (1–10 µM). * P≤0.01.
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Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4206466&req=5

pone-0111347-g004: Platelet fibrinogen binding in IPF patients and controls.A. Representative flow cytometry histogram demonstrating platelet fibrinogen binding under basal (unstimulated) conditions. B. Flow cytometry histogram demonstrating platelet fibrinogen binding following stimulation with 10 µM ADP. C. Percentage of platelets binding fibrinogen at basal levels and in response to the platelet agonists ADP (0.1–10 µM) or TFLLR (1–10 µM). * P≤0.01.
Mentions: The percentage of platelets binding fibrinogen was significantly higher in IPF patients compared with controls following stimulation with 0.1 µM and 1 µM ADP (0.1 µM ADP: 50.3%±8.9 versus 17.5%±6.1; p = <0.01; 1 µM ADP: 77.9%±4.6 versus 56.2%±6.5; p = <0.01). There was no significant difference in fibrinogen binding under basal (unstimulated) conditions (19.9%±6.0 versus 8.7%±3.2 respectively; p = 0.13). The increase in fibrinogen binding in IPF subjects following stimulation with TFLLR did not reach statistical significance (figure 4 and table S5 in file S1).

Bottom Line: Platelet P-selectin expression was significantly greater in IPF patients than controls following stimulation with 0.1 µM ADP (1.9% positive ±0.5 (mean ± SEM) versus 0.7%±0.1; p = 0.03), 1 µM ADP (9.8%±1.3 versus 3.3%±0.8; p<0.01) and 10 µM ADP (41.3%±4.2 versus 22.5%±2.6; p<0.01).Re-suspension of control platelets in plasma taken from subjects with IPF resulted in increased platelet activation compared to control plasma.IPF patients exhibit increased platelet reactivity compared with controls.

View Article: PubMed Central - PubMed

Affiliation: Centre for Cardiovascular and Metabolic Research, Hull York Medical School, Cottingham, United Kingdom.

ABSTRACT

Introduction: Idiopathic Pulmonary Fibrosis (IPF) is a progressive, incurable fibrotic interstitial lung disease with a prognosis worse than many cancers. Its pathogenesis is poorly understood. Activated platelets can release pro-fibrotic mediators that have the potential to contribute to lung fibrosis. We determine platelet reactivity in subjects with IPF compared to age-matched controls.

Methods: Whole blood flow cytometry was used to measure platelet-monocyte aggregate formation, platelet P-selectin expression and platelet fibrinogen binding at basal levels and following stimulation with platelet agonists. A plasma swap approach was used to assess the effect of IPF plasma on control platelets.

Results: Subjects with IPF showed greater platelet reactivity than controls. Platelet P-selectin expression was significantly greater in IPF patients than controls following stimulation with 0.1 µM ADP (1.9% positive ±0.5 (mean ± SEM) versus 0.7%±0.1; p = 0.03), 1 µM ADP (9.8%±1.3 versus 3.3%±0.8; p<0.01) and 10 µM ADP (41.3%±4.2 versus 22.5%±2.6; p<0.01). Platelet fibrinogen binding was also increased, and platelet activation resulted in increased platelet-monocyte aggregate formation in IPF patients. Re-suspension of control platelets in plasma taken from subjects with IPF resulted in increased platelet activation compared to control plasma.

Conclusions: IPF patients exhibit increased platelet reactivity compared with controls. This hyperactivity may result from the plasma environment since control platelets exhibit increased activation when exposed to IPF plasma.

Show MeSH
Related in: MedlinePlus