Elsevier

Modern Pathology

Volume 21, Issue 3, March 2008, Pages 297-307
Modern Pathology

Article
Aberrant fibrillin-1 expression in early emphysematous human lung: a proposed predisposition for emphysema

https://doi.org/10.1038/modpathol.3801004Get rights and content
Under an Elsevier user license
open archive

Abstract

Parenchymal destruction, airspace enlargement, and loss of elasticity are hallmarks of pulmonary emphysema. Although the basic mechanism is unknown, there is a consensus that malfunctioning of the extracellular matrix is a major contributor to the pathogenesis of emphysema. In this study, we analyzed the expression of the elastic fiber protein fibrillin-1 in a large number (n=69) of human lung specimens with early-onset emphysema. Specimens were morphologically characterized by the Destructive Index, the Mean Linear Intercept, and the Panel Grading. We observed a strong correlation (P<0.001) of aberrant fibrillin-1 staining with the degree of destruction of lung parenchyma (r=0.71), airspace enlargement (r=0.47), and emphysema-related morphological abnormalities (r=0.69). There were no obvious correlations with age and smoking behavior. Staining for three other extracellular matrix components (type I collagen, type IV collagen, and laminin) was not affected. The aberrant fibrillin-1 staining observed in this study is similar to that observed in Marfan syndrome, a syndrome caused by mutations in the gene encoding fibrillin-1. Strikingly, emphysema is noticed in a number of Marfan patients. This, together with the notion that disruption of the fibrillin-1 gene in mice results in emphysematous lesions, makes fibrillin-1 a strong candidate to be involved in the etiology and pathogenesis of emphysema.

pulmonary emphysema
lung
immunohistochemistry
fibrillin-1
elastic fiber
microfibril

Cited by (0)

Disclosure/conflict of interest The authors have declared no conflict of interest.

*

These authors contributed equally to this work.