Increased Fibronectin Expression in Lung in the Setting of Chronic Alcohol Abuse

Authors

  • Ellen L. Burnham,

    1. University of Colorado at Denver Health Sciences Center, Denver, Colorado, and
    Search for more papers by this author
  • Marc Moss,

    1. University of Colorado at Denver Health Sciences Center, Denver, Colorado, and
    Search for more papers by this author
  • Jeffrey D. Ritzenthaler,

    1. Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, Emory University School of Medicine, Atlanta, Georgia
    2. Atlanta Veterans Affairs Medical Center, Atlanta, Georgia
    Search for more papers by this author
  • Jesse Roman

    1. Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, Emory University School of Medicine, Atlanta, Georgia
    2. Atlanta Veterans Affairs Medical Center, Atlanta, Georgia
    Search for more papers by this author

  • This work was supported by Grants K23AA013918, P50AA013757, and DAMD17-02-1-0179.

Reprint requests: Ellen L. Burnham, MD, Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Health Sciences Center, 4200 E. Ninth Ave., Room 5525, C272, Denver, CO 80262; Fax: 303-315-1356; E-mail: Ellen.Burnham@uchsc.edu

Abstract

Rationale: The incidence and severity of the acute respiratory distress syndrome (ARDS) is increased in individuals who abuse alcohol. One possible mechanism by which alcohol increases susceptibility to acute lung injury is through alterations in alveolar macrophage function and induction of tissue remodeling activity. Our objective was to determine whether alcohol abuse, independent of other comorbidities, alters fibronectin and metalloproteinase gene expression in alveolar macrophages and in epithelial lining fluid (ELF) of the lung.

Methods: Otherwise healthy subjects with alcohol abuse (n=21) and smoking-matched controls (n=17) underwent bronchoalveolar lavage. Alveolar macrophage fibronectin and matrix metalloproteinase (MMP) mRNA expression were measured via reverse transcription-polymerase chain reaction. The supernatant from cultured alveolar macrophages and lung ELF were tested for their ability to induce fibronectin and MMP-9 gene transcription in cell-based assays.

Results: Alveolar macrophages from subjects with alcohol abuse demonstrated increased fibronectin mRNA expression (p<0.001), and their ELF also elicited more fibronectin gene transcription in lung fibroblasts compared with controls (p<0.001). In contrast, alveolar macrophages from subjects with alcohol abuse had decreased MMP-9 and MMP-2 mRNA expression (p<0.03 and p<0.005, respectively). Similarly, the supernatant (p<0.001) and ELF (p<0.01) from these subjects induced less MMP-9 gene transcription in THP-1 cells.

Discussion: Alcohol abuse is associated with increased fibronectin mRNA expression in alveolar macrophages and increased fibronectin-inducing activity in the ELF. This appears to be a specific effect as other tissue remodeling genes, such as MMPs, were not equally affected. These findings suggest activation of tissue remodeling that may contribute to the increased susceptibility for the ARDS observed in alcoholism.

Ancillary