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

Crooks, Michael G.; Fahim, Ahmed; Naseem, Khalid M.; Morice, Alyn H.; Hart, Simon P.

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.

Citation

Crooks, M. G., Fahim, A., Naseem, K. M., Morice, A. H., & Hart, S. P. (2014). Increased platelet reactivity in idiopathic pulmonary fibrosis is mediated by a plasma factor. PLoS ONE, 9(10), Article ARTN e111347. https://doi.org/10.1371/journal.pone.0111347

• Journal Article Type: Article
• Acceptance Date: Sep 23, 2014
• Online Publication Date: Oct 22, 2014
• Publication Date: Oct 22, 2014
• Deposit Date: Mar 16, 2017
• Publicly Available Date: Mar 16, 2017
• Journal: PLoS One
• Print ISSN: 1932-6203
• Publisher: Public Library of Science
• Peer Reviewed: Peer Reviewed
• Volume: 9
• Issue: 10
• Article Number: ARTN e111347
• DOI: https://doi.org/10.1371/journal.pone.0111347
• Keywords: Fibrosis; Interstitial Lung Disease; Monocyte; Platelet; P-selectin
• Public URL: https://hull-repository.worktribe.com/output/449711
• Publisher URL: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0111347
• Additional Information: This is a copy of an open access article published in PLoS One, 2014, v.9 issue 10.
• Contract Date: Mar 16, 2017