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Am J Physiol Lung Cell Mol Physiol (July 3, 2003). doi:10.1152/ajplung.00074.2003
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Submitted on March 13, 2003
Accepted on June 30, 2003

CIGARETTE SMOKE EXPOSURE POTENTIATES BLEOMYCIN-INDUCED LUNG FIBROSIS IN GUINEA PIGS

Jose Cisneros-Lira1, Miguel Gaxiola2, Carlos Ramos2, Moises Selman2, and Annie Pardo3*

1 Facultad de Ciencias, Universidad Nacional Autonoma de Mexico, Mexico, DF, Mexico; Unidad de Investigacion, Instituto Nacional de Enfermedades Respiratorias, Mexico, DF, Mexico
2 Unidad de Investigacion, Instituto Nacional de Enfermedades Respiratorias, Mexico, DF, Mexico
3 Facultad de Ciencias, Universidad Nacional Autonoma de Mexico, Mexico, DF, Mexico

* To whom correspondence should be addressed. E-mail: aps{at}hp.fciencias.unam.mx.

The role of tobacco smoking in the development and outcome of pulmonary fibrosis is uncertain. To approach the effects of cigarette smoke on bleomycin-induced lung fibrosis, five groups of guinea pigs were studied: 1) controls (C); 2) instilled with bleomycin (B); 3) exposed to tobacco smoke for 6 weeks (TS); 4) bleomycin instillation plus tobacco smoke exposure for 6 weeks (B+TS); 5) tobacco smoke exposure for 6 weeks and bleomycin after smoking (TS/B). Guinea pigs receiving bleomycin and tobacco smoke exposure exhibited higher fibrotic lesions including a significant increase in the number of positive alpha-smooth muscle actin cells compared to bleomycin alone (B+TS: 3.4±1.2%; TS/B: 3.7±1.5%; B: 2.3±1.5%; p<0.01). However, only TS/B group reached a significant increase in lung collagen compared to bleomycin group (TS/B: 3.5±0.7; B±TS: 2.9±0.4; B: 2.4±0.2 mg hydroxyproline/lung p<0.01). Bronchoalveolar lavage (BAL) from TS/B showed increased number of eosinophils, and higher levels of IL-4 and TIMP-2 (p<0.01 for all comparisons), and induced a significant increase in fibroblast proliferation (p<0.05). Importantly, smoke exposure alone induced an increase in BAL neutrophils, MMP-9, and fibroblast proliferation compared to controls suggesting that tobacco-smoke creates a profibrotic milieu that may contribute to the increased bleomycin-induced fibrosis.




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