Robbesom Antoine A, Koenders Mieke M J F, Smits Nicole C, Hafmans Theo, Versteeg Elly M M, Bulten Johan, Veerkamp Jacques H, Dekhuijzen P N Richard, van Kuppevelt Toin H
Department of Biochemistry, Radboud University Nijmegen Medical Center, Nijmegen Center for Molecular Life Sciences, Nijmegen, The Netherlands.
Mod Pathol. 2008 Mar;21(3):297-307. doi: 10.1038/modpathol.3801004. Epub 2007 Dec 14.
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.
