LPS-Induced Lung Platelet Recruitment Occurs Independently from Neutrophils, PSGL-1, and P-selectin

Simon J. Cleary, Carl Hobbs, Richard Amison, Stephanie Arnold, Blaze G. O'Shaughnessy, Emma Lefrançais, Beñat Mallavia, Mark R. Looney, Clive P. Page, Simon C. Pitchford

Research output: Contribution to journalArticlepeer-review

35 Citations (Scopus)
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Abstract

Platelets are recruited to inflammatory foci and contribute to host defence and inflammatory responses. Compared to platelet recruitment in hemostasis and thrombosis, the mechanisms of platelet recruitment in inflammation and host defence are poorly understood. Neutrophil recruitment to lung airspaces following inhalation of bacterial LPS requires platelets and PSGL-1 in mice. Given this association between platelets and neutrophils, we investigated whether recruitment of platelets to lungs of mice following LPS inhalation was dependent on PSGL-1, P-selectin, or interaction with neutrophils. BALB/c mice were administered intranasal LPS (O55:B5, 5 mg/kg) and 48 hours later lungs were collected, and platelets and neutrophils were quantified in tissue sections by immunohistochemistry. The effects of functional blocking antibody treatments targeting the platelet-neutrophil adhesion molecules P-selectin, or PSGL-1, or treatment with a neutrophil depleting antibody targeting Ly6G, were tested on the extent of LPS-induced lung platelet recruitment. Separately in Pf4-Cre×mTmG mice, two-photon intravital microscopy was used to image platelet adhesion in live lungs. Inhalation of LPS caused both platelet and neutrophil recruitment to the lung vasculature. However, decreasing lung neutrophil recruitment by blocking PSGL-1, P-selectin, or depleting blood neutrophils had no effect on lung platelet recruitment. Lung intravital imaging revealed increased adhesion of platelets in the lung microvasculature which was not associated with thrombus formation. In conclusion, platelet recruitment to lungs in response to LPS occurs through mechanisms distinct from those mediating neutrophil recruitment, or the occurrence of pulmonary emboli.
Original languageEnglish
Pages (from-to)232-243
Number of pages12
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume61
Issue number2
Early online date15 Feb 2019
DOIs
Publication statusPublished - 1 Aug 2019

Keywords

  • LPS
  • lungs
  • neutrophils
  • platelets
  • recruitment

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