OROPHARYNGEAL ASPIRATION OF A SILICA SUSPENSION PRODUCES A SUPERIOR MODEL OF SILICOSIS IN THE MOUSE WHEN COMPARED TO INTRATRACHEAL INSTILLATION
- 1 January 2006
- journal article
- research article
- Published by Informa UK Limited in Experimental Lung Research
- Vol. 32 (5), 181-199
- https://doi.org/10.1080/01902140600817465
Abstract
Instillation of crystalline silica into the lungs of mice is a common experimental model of pulmonary fibrosis. Typically, a suspension of silica in saline is injected into the trachea via intubation or surgical tracheostomy. These techniques require a high degree of technical skill, have a lengthy training period, and can suffer from a high failure rate. In oropharyngeal aspiration, a droplet of liquid is placed in the animal’s mouth while simultaneously holding its tongue (to block the swallow reflex) and pinching its nose shut, forcing it to breathe through its mouth, aspirating the liquid. To determine whether oropharyngeal aspiration (OA) could replace intratracheal instillation (IT) in a model of silica-induced fibrosis, a comparison was performed. Crystalline silica was introduced into the lungs of male C57BL/6 mice by the IT or OA procedure, and the resulting inflammation and fibrosis was assessed after 3 weeks. IT and OA instillation of silica both resulted in neutrophilic inflammation and fibrotic changes including interstitial fibrosis and dense fibrotic foci. Mice treated via IT demonstrated a few large lesions proximal to conducting airways with little involvement of the distal parenchyma and large inter-animal variability. In contrast, OA resulted in a diffuse pathology with numerous fibrotic foci distributed throughout the lung parenchyma, which is more representative of human fibrotic lung disease. OA, but not IT treated mice exhibited significantly increased lung collagen content. Furthermore, the inter-animal variability within the OA group was significantly less than in the IT group. Oropharyngeal aspiration should be considered as an alternative to intratracheal instillation of silica and other particulates in studies of respiratory toxicity and lung disease.Keywords
This publication has 43 references indexed in Scilit:
- Targeting Viral-Mediated Transduction to the Lung Airway Epithelium with the Anti-inflammatory Cationic Lipid Dexamethasone–SpermineMolecular Therapy, 2005
- Role of Inducible Nitric Oxide Synthase-Derived Nitric Oxide in Silica-Induced Pulmonary Inflammation and FibrosisJournal of Toxicology and Environmental Health, Part A, 2004
- Efficacy of a Technique for Exposing the Mouse Lung to Particles Aspirated from the PharynxJournal of Toxicology and Environmental Health, Part A, 2003
- Tracking the tissue distribution of marker dye following intranasal delivery in mice and chinchillas: a multifactorial analysis of parameters affecting nasal retentionVaccine, 2002
- Increased expression of matrix metalloproteinase in Clara cell-ablated mice inhaling crystalline silica.Environmental Health Perspectives, 2001
- Immunophenotyping of Lymphocytes in the Lung Interstitium and Expression of Osteopontin and Interleukin-2 Mrnas In Two Different Murine Models of Pulmonary FibrosisExperimental Lung Research, 1998
- Immune-inflammatory functions of fibroblastsEuropean Respiratory Journal, 1994
- Method for determining the lung burden of talc in rats and mice after inhalation exposure to talc aerosolsJournal of Applied Toxicology, 1985
- The distribution of dust in the rat lung following administration by inhalation and by single intratracheal instillationEnvironmental Research, 1985
- Hexachrome Modification of Movat's StainStain Technology, 1976