Intranasal versus intratracheal exposure to lipopolysaccharides in a murine model of acute respiratory distress syndrome

Fatemeh Khadangi,Annette Robichaud,Marie-Josée Beaulieu,Mathieu Morissette,Ynuk Bossé,Magali Boucher,David Brunet,Cyndi Henry,Sophie Tremblay-Pitre,Anne-Sophie Forgues,Alexis Dufour-Mailhot,Liah Fereydoonzad

doi:10.1038/s41598-021-87462-x

Fatemeh Khadangi, Annette Robichaud + Show 10 more

Open Access

https://doi.org/10.1038/s41598-021-87462-x

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Abstract

Due to frequent and often severe lung affections caused by COVID-19, murine models of acute respiratory distress syndrome (ARDS) are increasingly used in experimental lung research. The one induced by a single lipopolysaccharide (LPS) exposure is practical. However, whether it is preferable to administer LPS intranasally or intratracheally remains an open question. Herein, female C57Bl/6 J mice were exposed intranasally or intratracheally to one dose of either saline or 3 mg/kg of LPS. They were studied 24 h later. The groups treated with LPS, either intranasally or intratracheally, exhibited a pronounced neutrophilic inflammation, signs of lung tissue damage and protein extravasation into the alveoli, and mild lung dysfunction. The magnitude of the response was generally not different between groups exposed intranasally versus intratracheally. However, the variability of some the responses was smaller in the LPS-treated groups exposed intranasally versus intratracheally. Notably, the saline-treated mice exposed intratracheally demonstrated a mild neutrophilic inflammation and alterations of the airway epithelium. We conclude that an intranasal exposure is as effective as an intratracheal exposure in a murine model of ARDS induced by LPS. Additionally, the groups exposed intranasally demonstrated less variability in the responses to LPS and less complications associated with the sham procedure.

Highlights

Due to frequent and often severe lung affections caused by COVID-19, murine models of acute respiratory distress syndrome (ARDS) are increasingly used in experimental lung research
Since a fraction of SARS-CoV-2-infected patients degenerates into A RDS2,3, animal models of ARDS will be increasingly used in experimental lung research
This was mainly driven by an increased percentage of neutrophils, and a corresponding decrease in the percentage of macrophages, in the IT-exposed group versus the IN-exposed group treated with saline (Fig. 2B and C)

Summary

Introduction

Due to frequent and often severe lung affections caused by COVID-19, murine models of acute respiratory distress syndrome (ARDS) are increasingly used in experimental lung research. The outcomes can be measured with relative ease and represent relevant features of human ARDS, including neutrophilic inflammation, signs of damage to the alveolar capillary barrier, lung tissue injury, and physiological d ysfunction[6,9]. It is a good model for both pragmatic and scientific reasons. The procedures to set out the murine model of ARDS induced by LPS are not fully standardized and some specific technicalities were shown to differ among previous users One such unresolved technical question is to whether LPS should be administered intranasally or intratracheally. We compare the intranasal (IN) and intratracheal (IT) routes of administration in terms of both the magnitude and the variability of the response to LPS for several outcomes that are traditionally used to assess ARDS in animal m odels[9] (Fig. 1)

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