This Article Order Full text via Infotrieve Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Fukuda, Y. Articles by Crystal, R. G. Search for Related Content PubMed PubMed Citation Articles by Fukuda, Y. Articles by Crystal, R. G.

American Journal of Pathology, Vol 118, 452-475, Copyright © 1985 by American Society for Investigative Pathology

REGULAR ARTICLES

Patterns of pulmonary structural remodeling after experimental paraquat toxicity. The morphogenesis of intraalveolar fibrosis

Y Fukuda, VJ Ferrans, CI Schoenberger, SI Rennard and RG Crystal

For a study of the evolution of interstitial and intraalveolar fibrosis, ultrastructural and immunohistochemical observations were made of the lungs of 16 cynomolgous monkeys given 1 or 2 injections of 10 mg/kg of paraquat and sacrificed 2 days to 8 weeks later. At 2-3 days, alveolar epithelial cells were denuded in many areas, and fibronectin was conspicuous in alveolar spaces. At 1 week, fibroblasts and inflammatory cells were migrating through gaps in the denuded epithelial basement membranes; Type II cells were regenerating in some areas. At 3-4 weeks, alveoli developing intraalveolar fibrosis contained many myofibroblasts, collagen fibrils, and small elastic fibers; fibrotic alveolar walls were lined by metaplastic squamous cells and bronchiolar epithelial cells. Spiraling collagen fibrils were found in interstitium but not in alveolar spaces, which suggests that they were formed from breakdown of collagen. Newly formed intraalveolar collagen was mainly Type I. At 8 weeks, intraalveolar fibrosis had led to extensive remodeling, with new glandlike alveoli lined by Type II cells; alveoli without intraalveolar fibrosis had more normal architecture. Thus, intraalveolar fibrosis in paraquattreated lung is mediated by intraalveolar migration of interstitial cells, through gaps in the epithelial basement membranes, after epithelial injury. This is followed by connective tissue synthesis on the luminal side of the epithelial basement membrane, by differentiation of interstitial cells into myofibroblasts and smooth-muscle cells, by incorporation of areas of intraalveolar fibrosis into the interstitium, and by coalescence of alveolar walls. Intraalveolar fibrosis is more important than interstitial fibrosis in the structural remodeling that occurs in paraquattreated lung, because it results in obliteration of alveoli, coalescence of alveolar walls, and loss of functional alveolar- capillary units.

This article has been cited by other articles:

				N. Odajima, T. Betsuyaku, Y. Nasuhara, and M. Nishimura Loss of Caveolin-1 in Bronchiolization in Lung Fibrosis J. Histochem. Cytochem., September 1, 2007; 55(9): 899 - 909. [Abstract] [Full Text] [PDF]

				J-F. Cordier Cryptogenic organising pneumonia. Eur. Respir. J., August 1, 2006; 28(2): 422 - 446. [Abstract] [Full Text] [PDF]

				Y. Terasaki Epimorphin in Bleomycin-Induced Pulmonary Fibrosis in Mice Chest, July 1, 2001; 120(2007): 30S - 32S. [Full Text] [PDF]

				I. GOLDSTEIN, M.-T. BUGHALO, C.-H. MARQUETTE, G. LENAOUR, Q. LU, J.-J. ROUBY, and the Experimental ICU Study Group Mechanical Ventilation-induced Air-Space Enlargement during Experimental Pneumonia in Piglets Am. J. Respir. Crit. Care Med., March 15, 2001; 163(4): 958 - 964. [Abstract] [Full Text]

				M. DOHI, T. HASEGAWA, K. YAMAMOTO, and B. C. MARSHALL Hepatocyte Growth Factor Attenuates Collagen Accumulation in a Murine Model of Pulmonary Fibrosis Am. J. Respir. Crit. Care Med., December 1, 2000; 162(6): 2302 - 2307. [Abstract] [Full Text]

				M. SUGA, K. IYONAGA, T. OKAMOTO, Y. GUSHIMA, H. MIYAKAWA, T. AKAIKE, and M. ANDO Characteristic Elevation of Matrix Metalloproteinase Activity in Idiopathic Interstitial Pneumonias Am. J. Respir. Crit. Care Med., November 1, 2000; 162(5): 1949 - 1956. [Abstract] [Full Text]

				K. C. Fang Mesenchymal Regulation of Alveolar Repair in Pulmonary Fibrosis Am. J. Respir. Cell Mol. Biol., August 1, 2000; 23(2): 142 - 145. [Full Text]

				Y. Terasaki, Y. Fukuda, M. Ishizaki, and N. Yamanaka Increased Expression of Epimorphin in Bleomycin-Induced Pulmonary Fibrosis in Mice Am. J. Respir. Cell Mol. Biol., August 1, 2000; 23(2): 168 - 174. [Abstract] [Full Text]

				A. PARDO, R. BARRIOS, M. GAXIOLA, L. SEGURA-VALDEZ, G. CARRILLO, A. ESTRADA, M. MEJÍA, and M. SELMAN Increase of Lung Neutrophils in Hypersensitivity Pneumonitis Is Associated with Lung Fibrosis Am. J. Respir. Crit. Care Med., May 1, 2000; 161(5): 1698 - 1704. [Abstract] [Full Text]

				C.-H. Kao, J.-F. Hsieh, Y.-J. Ho, D.-Z. Hung, T.-J. Lin, and H.-J. Ding Acute Paraquat Intoxication: Using Nuclear Pulmonary Studies to Predict Patient Outcome Chest, September 1, 1999; 116(3): 709 - 714. [Abstract] [Full Text] [PDF]

				M.T. Corasaniti, G. Bagetta, P. Rodino, S. Gratteri, and G. Nistico Neurotoxic Effects Induced by Intracerebral and Systemic Injection of Paraquat in Rats Human and Experimental Toxicology, January 1, 1992; 11(6): 535 - 539. [Abstract] [PDF]