Effects of different routes of endotoxin injury on barrier function in alcoholic lung syndrome

• Published in: Alcohol (Fayetteville, N.Y.) N.Y.), 2019-11, Vol.80, p.81-89
• Main Authors: Smith, Prestina, Jeffers, Lauren A., Koval, Michael
• Format: Article
• Language: English
• Subjects: Alcohol; Alcohol use; Alcoholism; Alcohols; Alveoli; ARDS; Barrier function; Edema; Endotoxemia; Endotoxin; Endotoxins; Ethanol; Experiments; Flooding; Ingestion; Laboratory animals; Lipopolysaccharide; Lipopolysaccharides; Lungs; Microvasculature; Morphometry; Mortality; Pathology; Permeability; Pneumonia; Pulmonary vasculature; Respiratory distress syndrome; Risk factors; Sepsis; Tight junction; Trachea
• ISSN: 0741-8329; 1873-6823
• DOI: 10.1016/j.alcohol.2018.08.007

In the lung, chronic alcohol consumption is a risk factor for acute respiratory distress syndrome (ARDS), a disorder that can be fatal due to airspace flooding. The severity of pulmonary edema is controlled by multiple barriers, and in particular the alveolar epithelial barrier and pulmonary microvasculature. However, to date, the effects of chronic alcohol ingestion on both of these barriers in the lung has not been directly and simultaneously measured. In addition the effects of alcohol on systemic, indirect lung injury versus direct injury have not been compared. In this study, we used tissue morphometry and Evans Blue permeability assays to assess the effects of alcohol and endotoxemia injury on pulmonary barrier function comparing intraperitoneal (IP) administration of lipopolysaccharide (LPS) to intratracheal (IT) administration. Consistent with previous reports, we found that in alcohol-fed mice, the alveolar barrier was impaired, allowing Evans Blue to permeate into the airspaces. Moreover, IT administered LPS caused a significant breach of both the alveolar epithelial and vascular barriers in alcohol-fed mice, whereas the endothelial barrier was less affected in response to IP administered LPS. The alveolar barrier of control mice remained intact for both IP and IT administered LPS. However, both injuries caused significant interstitial edema, independently of whether the mice were fed alcohol or not. These data suggest that in order to properly target pulmonary edema due to alcoholic lung syndrome, both the alveolar and endothelial barriers need to be considered as well as the nature of the "second hit" that initiates ARDS. •Chronic alcohol has a deleterious effect on lung epithelial barrier function in the absence of injury.•Alcohol and mild intraperitoneal or intratracheal endotoxemia independently increase interstitial edema.•In alcohol-fed mice, the pulmonary microvascular barrier is impaired following intratracheal lipopolysaccharide injury.•Both the alveolar epithelial and pulmonary endothelial barriers should be considered in targeting alcoholic lung syndrome.