Development of interstitial lung fibrosis by long-term treatment with collagen breakdown products in rabbits.
We recently demonstrated that collagen breakdown products derived from elastase digestion (CDP) can stimulate "in vivo" lung collagen synthesis. The present work deals with the morphological and biochemical characteristics of an experimental model of lung fibrosis developed in rabbit by long-term treatment with CDP. Stimulation of collagen synthesis by CDP resulted in a significant thickening of alveolar septa due to accumulation of fibroblasts and a marked deposition of collagen fibrils as revealed by light as well as electron microscopy. Biochemical analysis confirmed the increase in lung collagen deposition. Total collagen content as determined by hydroxy-proline analysis was increased in CDP-treated animals of about 56% in respect to control animals. A relative increase of type I collagen in respect to type III was also observed. An additional interesting observation was a progressive hyperplasia of type II pneumocytes. Unlike other experimental models of lung fibrosis, the collagen deposition in our condition is not preceded or associated with inflammatory or degenerative processes. This fact renders this model very suitable to study matrix-cell interactions in pulmonary fibrogenesis.
Gardi
C
C
Institute of General Pathology, University of Siena, Italy.
Pacini
A
A
de Santi
M M
MM
Calzoni
P
P
Viti
A
A
Corradeschi
F
F
Lungarella
G
G
D000704:Analysis of Variance; D000818:Animals; D003094:Collagen / Q000378:metabolism* / Q000494:pharmacology; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D005109:Extracellular Matrix / Q000378:metabolism; D008168:Lung / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D010196:Pancreatic Elastase / Q000378:metabolism; D010455:Peptides / Q000008:administration & dosage / Q000494:pharmacology; D011658:Pulmonary Fibrosis / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D011817:Rabbits
D010455:Peptides; D003094:Collagen; D010196:Pancreatic Elastase