TY - JOUR
T1 - Platelet depletion impairs host defence to pulmonary infection with Pseudomonas aeruginosa in mice
AU - Amison, Richard
AU - O'Shaughnessy, Blaze G.
AU - Arnold, Stephanie
AU - Cleary, Simon J.
AU - Nandi, Manasi
AU - Pitchford, Simon C.
AU - Bragonzi, Alessandra
AU - Page, Clive P.
N1 - Publisher Copyright:
Copyright © 2018 by the American Thoracic Society
PY - 2018/3
Y1 - 2018/3
N2 - Platelets have been implicated in pulmonary inflammatory cell recruitment following exposure to allergic and non-allergic stimuli, but little is known about the role of platelets in response to pulmonary infection with Pseudomonas aeruginosa (P. aeruginosa). In this study, we have investigated the impact of the experimental depletion of circulating platelets on a range of inflammatory and bacterial parameters, and their subsequent impact on mortality in a murine model of pulmonary infection with P. aeruginosa. P. aeruginosa infection in mice induced a mild but significant state of peripheral thrombocytopenia in addition to pulmonary platelet accumulation. Increased platelet activation was detected in infected mice through increased levels of the platelet derived mediators PF-4 and β-TG in bronchoalveolar lavage fluid (BALF) and blood plasma. In mice depleted of circulating platelets, pulmonary neutrophil recruitment was significantly reduced 24 hours’ post infection, whilst the incidence of systemic dissemination of bacteria was significantly increased compared to non-platelet depleted control mice. Furthermore, mortality rates were increased in bacterial infected mice depleted of circulating platelets. This work demonstrates a role for platelets in the host response towards a gram-negative bacterial respiratory infection.
AB - Platelets have been implicated in pulmonary inflammatory cell recruitment following exposure to allergic and non-allergic stimuli, but little is known about the role of platelets in response to pulmonary infection with Pseudomonas aeruginosa (P. aeruginosa). In this study, we have investigated the impact of the experimental depletion of circulating platelets on a range of inflammatory and bacterial parameters, and their subsequent impact on mortality in a murine model of pulmonary infection with P. aeruginosa. P. aeruginosa infection in mice induced a mild but significant state of peripheral thrombocytopenia in addition to pulmonary platelet accumulation. Increased platelet activation was detected in infected mice through increased levels of the platelet derived mediators PF-4 and β-TG in bronchoalveolar lavage fluid (BALF) and blood plasma. In mice depleted of circulating platelets, pulmonary neutrophil recruitment was significantly reduced 24 hours’ post infection, whilst the incidence of systemic dissemination of bacteria was significantly increased compared to non-platelet depleted control mice. Furthermore, mortality rates were increased in bacterial infected mice depleted of circulating platelets. This work demonstrates a role for platelets in the host response towards a gram-negative bacterial respiratory infection.
KW - Host defense
KW - Host-pathogen interactions
KW - Platelets
KW - Pseudomonas aeruginosa
UR - http://www.scopus.com/inward/record.url?scp=85044004157&partnerID=8YFLogxK
U2 - 10.1165/rcmb.2017-0083OC
DO - 10.1165/rcmb.2017-0083OC
M3 - Article
C2 - 28957635
AN - SCOPUS:85044004157
SN - 1044-1549
VL - 58
SP - 331
EP - 340
JO - American Journal of Respiratory Cell and Molecular Biology
JF - American Journal of Respiratory Cell and Molecular Biology
IS - 3
ER -