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Human platelet activation by Escherichia coli: roles for FcγRIIA and integrin αIIbβ3

Watson, Callum N.; Cox, Dermot; Watson, Steve P.; Arman, Mònica; Henderson, Ian R.; Kerrigan, Steven W.

Authors

Callum N. Watson

Dermot Cox

Steve P. Watson

Mònica Arman

Ian R. Henderson

Steven W. Kerrigan



Abstract

Gram-negative Escherichia coli cause diseases such as sepsis and hemolytic uremic syndrome in which thrombotic disorders can be found. Direct platelet–bacterium interactions might contribute to some of these conditions; however, mechanisms of human platelet activation by E. coli leading to thrombus formation are poorly understood. While the IgG receptor FcγRIIA has a key role in platelet response to various Gram-positive species, its role in activation to Gram-negative bacteria is poorly defined. This study aimed to investigate the molecular mechanisms of human platelet activation by E. coli, including the potential role of FcγRIIA. Using light-transmission aggregometry, measurements of ATP release and tyrosine-phosphorylation, we investigated the ability of two E. coli clinical isolates to activate platelets in plasma, in the presence or absence of specific receptors and signaling inhibitors. Aggregation assays with washed platelets supplemented with IgGs were performed to evaluate the requirement of this plasma component in activation. We found a critical role for the immune receptor FcγRIIA, αIIbβ3, and Src and Syk tyrosine kinases in platelet activation in response to E. coli. IgG and αIIbβ3 engagement was required for FcγRIIA activation. Moreover, feedback mediators adenosine 5’-diphosphate (ADP) and thromboxane A₂ (TxA₂) were essential for platelet aggregation. These findings suggest that human platelet responses to E. coli isolates are similar to those induced by Gram-positive organisms. Our observations support the existence of a central FcγRIIA-mediated pathway by which human platelets respond to both Gram-negative and Gram-positive bacteria.

Citation

Watson, C. N., Cox, D., Watson, S. P., Arman, M., Henderson, I. R., & Kerrigan, S. W. (2016). Human platelet activation by Escherichia coli: roles for FcγRIIA and integrin αIIbβ3. Platelets, 27(6), 535-540. https://doi.org/10.3109/09537104.2016.1148129

Acceptance Date Jan 22, 2016
Online Publication Date Mar 30, 2016
Publication Date Aug 17, 2016
Deposit Date May 16, 2016
Publicly Available Date May 16, 2016
Journal Platelets
Print ISSN 0953-7104
Electronic ISSN 1369-1635
Publisher Taylor & Francis
Peer Reviewed Peer Reviewed
Volume 27
Issue 6
Pages 535-540
DOI https://doi.org/10.3109/09537104.2016.1148129
Keywords Blood platelets, Escherichia coli, Fc gamma receptor IIA, Innate immunity, Thrombosis
Public URL https://hull-repository.worktribe.com/output/438189
Publisher URL http://www.tandfonline.com/doi/abs/10.3109/09537104.2016.1148129
Copyright Statement This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Additional Information Copy of article first published in: Platelets, 2016

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http://creativecommons.org/licenses/by/4.0/

Copyright Statement
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.





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