Alveolar type II cells from ethanol-fed rats produce a fibronectin-enriched extracellular matrix that promotes monocyte activation

• Type of Material: Article
• Authors: Lou Ann Brown, Emory University; Jeffrey D. Ritzenthaler, Emory University; David M Guidot, Emory University; Jesse Roman, Emory University
• Language: English
• Date: 2007-08
• Publisher: Elsevier Masson
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2007 Elsevier Inc. All rights reserved.
• License: Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.1016/j.alcohol.2007.04.009
• Title of Journal or Parent Work: Alcohol
• ISSN: 0741-8329
• Volume: 41
• Issue: 5
• Start Page: 317
• End Page: 324
• Grant/Funding Information: This work was also supported by the Department of Defense Grant DAMD17-02-1-0179 (JR).; This study was funded by NIH NIAAA grant R01 AA12197 (LAB), NIH NHLBI grant R01 HL67399 (LAB), and NIAAA Center Grant P50 AA 135757 (LAB, DMG and JR).
• Keywords: extracellular matrix; oxidant stress; tissue remodeling; lung injury
• Research Categories: Health Sciences, General

Abstract

Acute lung injury affects close to 200,000 people in the U.S. annually and leads to death in 40–50% of affected patients. Chronic ethanol abuse is thought to contribute to up to 40–50% of subjects who develop acute lung injury. We previously demonstrated in a rat model that chronic ethanol ingestion promoted acute lung injury and associated with chronic oxidant stress, activated matrix metalloproteinases, increased release of transforming growth factor-β, as well as increased expression and deposition of fibronectin, a matrix glycoprotein implicated in lung injury and repair. Since fibronectin can activate monocytes to increase proinflammatory cytokine expression, we hypothesized that generation of fibronectin-enriched matrices during chronic ethanol ingestion might contribute to the development of acute lung injury by stimulating unopposed inflammation. To test this hypothesis, we harvested alveolar type II cells from rats fed the Lieber DiCarli diet (6 wk; 36% of calories from ethanol). After 96 hours of culture, the matrices deposited ex vivo by the type II cells derived from ethanol-fed rats showed increased amounts of fibronectin protein as demonstrated by ELISA. When monocytic U937 cells were plated atop these matrices, there was increased expression of interleukin-1β. This stimulation was inhibited by antibodies against α5β1, a receptor that mediates many of the biological effects of fibronectin. We then tested whether antioxidants ameliorated these effects. Dietary supplements of the antioxidants N-acetylcysteine and Procysteine normalized matrix production by type II cells. Furthermore, the newly derived matrices did not stimulate interleukin-1β expression over control cells. These studies suggest that chronic ethanol exposure induces oxidant stress and activates lung tissue remodeling characterized by increased expression of fibronectin by alveolar type II cells. The newly deposited fibronectin-enriched matrices may stimulate the expression of proinflammatory cytokines in monocytic cells recruited to the lung after injury thereby explaining the priming effects of ethanol.