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

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.

Additive effects of orchiectomy and intermittent hypoxia on lung mechanics and inflammation in C57BL/6J male mice

“…Following whole body plethysmography, respiratory mechanics was assessed using the flexiVent system (SCIREQ) as previously described (Boucher et al., 2021; Khadangi et al., 2021; Mailhot‐Larouche et al ., 2018). The mice were anaesthetized with ketamine and xylazine (100 and 10 mg/kg).…”

Innate Lymphoid Cells Are Required to Induce Airway Hyperreactivity in a Murine Neutrophilic Asthma Model

“…LPS is often also used for murine models for acute lung injury also characterized by LPS-induced neutrophilic inflammation (40). However, the concentrations used in these models to induce acute lung injury are ten to fifty times more than used in this model (40)(41)(42) and airway hyperreactivity is often not included in these studies. Interestingly, Khadangi et al showed that no changes in respiratory mechanisms could be observed in their model used for acute lung injury (42).…”

“…However, the concentrations used in these models to induce acute lung injury are ten to fifty times more than used in this model (40)(41)(42) and airway hyperreactivity is often not included in these studies. Interestingly, Khadangi et al showed that no changes in respiratory mechanisms could be observed in their model used for acute lung injury (42). By lowering the dose of LPS, we tried to mimic several features of non-allergic asthma with neutrophilic inflammation such as AHR and neutrophilic inflammation.…”

Antioxidants as Therapeutic Agents in Acute Respiratory Distress Syndrome (ARDS) Treatment—From Mice to Men

“… Direct Lung Damage [ 17 , 22 , 23 ] Route of Application ARDS-Like Affects Antioxidant Approaches Already Used Ref. LPS [ 24 , 25 , 26 ] intranasal/intratracheal instillation lung accumulation of neutrophils, induction of proinflammatory cytokines NAC, SAMC [ 27 , 28 , 29 ] Bacteria [ 30 , 31 , 32 ] intratracheal instillation lung accumulation of neutrophils, induction of proinflammatory cytokines CDC [ 33 ] HCl [ 34 , 35 , 36 ] intratracheal instillation neutrophil infiltration, damage of alveolar/ vascular barrier apocynin, MitoTempo [ 37 , 38 ] Hyperoxia (HALI) [ 39 , 40 , 41 ] intratracheal …”