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

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.

• Authors: Antoine A Robbesom, Mieke M J F Koenders, Nicole C Smits, Theo Hafmans, Elly M M Versteeg, Johan Bulten, Jacques H Veerkamp, P N Richard Dekhuijzen, Toin H van Kuppevelt
• Journal: Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc (Mod Pathol) Vol. 21 Issue 3 Pg. 297-307 (Mar 2008) ISSN: 0893-3952 [Print] United States
• PMID: 18084245 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Extracellular Matrix Proteins
• FBN1 protein, human
• Fbn1 protein, mouse
• Fibrillin-1
• Fibrillins
• Microfilament Proteins

Topics

• Aged
• Extracellular Matrix Proteins (biosynthesis, genetics)
• Fibrillin-1
• Fibrillins
• Gene Expression Regulation
• Genetic Predisposition to Disease
• Humans
• Immunohistochemistry
• Lung (metabolism, pathology)
• Microfilament Proteins (biosynthesis, genetics)
• Middle Aged
• Pulmonary Emphysema (genetics, pathology, physiopathology)