Increased elastin production in experimental granulomatous lung disease.
In the normal, healthy lung, elastin production is restricted to periods of development and growth. However, elastin expression in the adult lung has been observed in some forms of pulmonary injury, including pulmonary fibrosis. Here, we report that elastin production is significantly increased within precise interstitial compartments of the lung in an experimental model of granulomatous lung disease. An increase in the number and volume of elastic fibers within the alveolar walls was apparent on histological examination of Verhoeff-van Gieson-stained sections of silicotic rat lungs. Quantitation of mature elastin cross-links indicated that silicosis was accompanied by a 17-fold increase in lung elastin content when compared with values from saline-treated controls. In situ hybridization for tropoelastin mRNA revealed that elastin production was absent from granulomatous lesions yet was prominent at nonfibrotic alveolar septal tips, where a high density of elastic fibers is seen in the normal lung. Immunohistochemistry indicated tropoelastin was being expressed by alpha-smooth muscle actin-containing cells. Transforming growth factor-beta was immunolocalized to granulomatous regions of the silicotic lung but was absent from regions showing increased tropoelastin expression. These data indicate that the reinitiation of tropoelastin gene expression is associated with granulomatous lung disease, and this expression leads to the aberrant accumulation of mature elastin in the lung.
Mariani
T J
TJ
Department of Internal Medicine, Washington University School of Medicine, Jewish Hospital, St. Louis, Missouri 63110, USA.
Crouch
E
E
Roby
J D
JD
Starcher
B
B
Pierce
R A
RA
D000199:Actins / Q000378:metabolism; D000818:Animals; D004549:Elastin / Q000096:biosynthesis*; D015870:Gene Expression; D006099:Granuloma / Q000378:metabolism* / Q000473:pathology; D008171:Lung Diseases / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009130:Muscle, Smooth; D011650:Pulmonary Alveoli / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012829:Silicosis / Q000378:metabolism / Q000473:pathology; D012995:Solubility; D014018:Tissue Distribution; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014333:Tropoelastin / Q000235:genetics / Q000378:metabolism
D000199:Actins; D016212:Transforming Growth Factor beta; D014333:Tropoelastin; D004549:Elastin