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Published on: February 14, 2017
Platelet proinflammatory activity in clinically stable patients with CF starts in early childhood
Alexander Sturm1, Helge Hebestreit, Corinne Koenig
1University Children's Hospital, 97080 Würzburg, Germany.
Insights
Platelets show increased inflammatory activity in cystic fibrosis (CF) patients from a young age, potentially worsening inflammation and tissue damage. However, their ability to form clots appears reduced in active CF inflammation.
Area of Science:
- Hematology
- Immunology
- Pulmonology
Background:
- Chronic inflammation is a hallmark of cystic fibrosis (CF).
- Platelets are implicated in inflammatory processes through cytokine release and leukocyte interactions.
Purpose of the Study:
- To investigate platelet proinflammatory and procoagulatory functions in CF patients.
- To assess how inflammation and age affect platelet function in CF.
Main Methods:
- Measured soluble CD62P, soluble CD40L, platelet-leukocyte aggregates, and platelet CD62P.
- Assessed PAC-1 binding to activated integrin alpha(IIb)beta(3) and CD41a expression.
Main Results:
- Elevated soluble CD62P and soluble CD40L in CF patients, independent of age or inflammation activity.
- Increased platelet-leukocyte aggregates in older CF patients.
- Reduced PAC-1 binding and CD41a exocytosis upon platelet activation in CF patients with active inflammation.
Conclusions:
- Platelets exhibit heightened proinflammatory activity in young CF patients, potentially contributing to inflammation and tissue damage.
- Platelet integrin alpha(IIb)beta(3) activation for clot formation is downregulated in CF, especially during active inflammation.
Background:
Early onset chronic inflammation is present in CF. Platelets may contribute to inflammation by cytokine release and interaction with leukocytes.
Methods:
Parameters of platelet proinflammatory function (soluble CD62P, soluble CD40L, the percentage of platelet-leukocyte aggregates, platelet CD62P) and platelet procoagulatory function (PAC-1-binding to activated integrin alpha(IIb)beta(3) and expression of integrin alpha(IIb)beta(3)=CD41a) were measured in patients and controls.
Results:
Levels of sCD62P, sCD40L were increased in CF irrespective of age and activity of inflammation. The number of platelet-leukocyte aggregates was elevated in older CF patients. PAC-1-binding to platelets decreased with growing activity of inflammation. Exocytosis of CD41a upon platelet activation was reduced.
Conclusion:
In CF, platelet proinflammatory activity is increased at very young age already and might promote inflammation and tissue damage. On the other hand, platelets seem to downregulate the activation of their most important integrin (alpha(IIb)beta(3)) for clot formation.
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