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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

The influence of the plasma environment on platelet function in IPF patients.Scatter plots (A,C,E,G) demonstrating platelet P-selectin expression (bars indicate means) and line graphs (B,D,F,H) showing the change in P-selectin expression of control platelets following incubation in autologous plasma, allogeneic control plasma, and IPF patient plasma at basal levels (A,B) and following stimulation with ADP 0.1 µM (C,D), 1 µM (E,F) and 10 µM (G,H).
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pone-0111347-g005: The influence of the plasma environment on platelet function in IPF patients.Scatter plots (A,C,E,G) demonstrating platelet P-selectin expression (bars indicate means) and line graphs (B,D,F,H) showing the change in P-selectin expression of control platelets following incubation in autologous plasma, allogeneic control plasma, and IPF patient plasma at basal levels (A,B) and following stimulation with ADP 0.1 µM (C,D), 1 µM (E,F) and 10 µM (G,H).

Mentions: We next examined whether the platelet hyperactivity observed in IPF was caused by a primary platelet defect or the plasma environment. Re-suspension of washed control platelets in plasma from IPF subjects led to elevated P-selectin expression when compared with platelets suspended in autologous control or allogeneic control plasma. IPF plasma increased P-selectin expression under both basal conditions (p<0.05) and following stimulation with ADP at concentrations of 0.1 and 1 µM (P≤0.01) (figure 5 and table S6 in file S1). Further analysis was performed to confirm the increase in platelet P-selectin expression seen in IPF plasma. From a baseline taken as the platelet P-selectin expression in the autologous control group, the increase in platelet P-selectin expression in the presence of IPF plasma was significantly greater than the allogeneic control group at basal levels and following stimulation with all concentrations of ADP (p<0.05).


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)

The influence of the plasma environment on platelet function in IPF patients.Scatter plots (A,C,E,G) demonstrating platelet P-selectin expression (bars indicate means) and line graphs (B,D,F,H) showing the change in P-selectin expression of control platelets following incubation in autologous plasma, allogeneic control plasma, and IPF patient plasma at basal levels (A,B) and following stimulation with ADP 0.1 µM (C,D), 1 µM (E,F) and 10 µM (G,H).
© Copyright Policy
Related In: Results  -  Collection

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

pone-0111347-g005: The influence of the plasma environment on platelet function in IPF patients.Scatter plots (A,C,E,G) demonstrating platelet P-selectin expression (bars indicate means) and line graphs (B,D,F,H) showing the change in P-selectin expression of control platelets following incubation in autologous plasma, allogeneic control plasma, and IPF patient plasma at basal levels (A,B) and following stimulation with ADP 0.1 µM (C,D), 1 µM (E,F) and 10 µM (G,H).
Mentions: We next examined whether the platelet hyperactivity observed in IPF was caused by a primary platelet defect or the plasma environment. Re-suspension of washed control platelets in plasma from IPF subjects led to elevated P-selectin expression when compared with platelets suspended in autologous control or allogeneic control plasma. IPF plasma increased P-selectin expression under both basal conditions (p<0.05) and following stimulation with ADP at concentrations of 0.1 and 1 µM (P≤0.01) (figure 5 and table S6 in file S1). Further analysis was performed to confirm the increase in platelet P-selectin expression seen in IPF plasma. From a baseline taken as the platelet P-selectin expression in the autologous control group, the increase in platelet P-selectin expression in the presence of IPF plasma was significantly greater than the allogeneic control group at basal levels and following stimulation with all concentrations of ADP (p<0.05).

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