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Radiolabelling and immunohistochemistry reveal platelet recruitment into lungs and platelet migration into airspaces following LPS inhalation in mice

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S. J. Cleary, F. Rauzi, E. Smyth, A. Correia, C. Hobbs, M. Emerson, C. P. Page, S. C. Pitchford

Original languageEnglish
Article number106660
JournalJournal of pharmacological and toxicological methods
Volume102
Early online date12 Dec 2019
DOIs
Accepted/In press1 Dec 2019
E-pub ahead of print12 Dec 2019
Published1 Mar 2020

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Abstract

Introduction: Platelets are under investigation for their role in host defence and inflammatory lung diseases and have been demonstrated to be recruited to the lung. However, the mechanisms and consequences of platelet recruitment into lungs are poorly understood. We have utilised a murine model to investigate the mechanisms of platelet involvement in lung inflammation induced by intranasal administration of LPS. Objectives: Our aim was to characterise lung platelet recruitment following LPS inhalation in mice using immunohistochemistry, and non-invasive and invasive radiolabelled platelet tracking techniques. Results: Intranasal administration of LPS caused an increase in lung platelet staining in lung tissue and elicited the recruitment of radiolabelled platelets into the lung. Prior to these responses in the lung, we observed an earlier decrease in blood platelet counts, temporally associated with platelet recruitment to the liver and spleen. Non-invasive measurements of thoracic radioactivity reflected changes in blood counts rather than extravascular lung platelet recruitment. However, both in situ counting of radiolabelled platelets and immunostaining for platelet surface markers showed LPS-induced increases in extravascular platelets into lung airspaces suggesting that some of the platelets recruited to the lung enter air spaces. Conclusions: Intranasal administration of LPS activates the innate immune response which includes a fall in peripheral blood platelet counts with subsequent platelet recruitment to the lung, spleen and liver, measured by immunohistochemistry and radiolabelling techniques.

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