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

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

Authors

Michael Crooks

Michael G. Crooks

Simon Hart

Ahmed Fahim

Alyn Morice

Khalid M. Naseem

Khalid Naseem

Alyn H. Morice

Simon P. Hart



Contributors

Carol Feghali-Bostwick
Editor

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; pā€Š=ā€Š0.03), 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), 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
Electronic 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.

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Publisher Licence URL
https://creativecommons.org/licenses/by/4.0/

Copyright Statement
© 2014 Crooks et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.





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