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This Article Full Text Full Text (PDF) All Versions of this Article: 285/4/L949    most recent 00074.2003v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science 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 ISI Web of Science (5) Citing Articles via Google Scholar Google Scholar Articles by Cisneros-Lira, J. Articles by Pardo, A. Search for Related Content PubMed PubMed Citation Articles by Cisneros-Lira, J. Articles by Pardo, A.

Cigarette smoke exposure potentiates bleomycin-induced lung fibrosis in guinea pigs

¹Facultad de Ciencias, Universidad Nacional Autónoma de México, Circuito Exterior S/N, Mexico City 04000; and ²Instituto Nacional de Enfermedades Respiratorias, Tlalpan 4502, Mexico City, Mexico

Submitted 13 March 2003 ; accepted in final form 30 June 2003

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, we studied five groups of guinea pigs: 1) controls, 2) instilled with bleomycin (B), 3) exposed to tobacco smoke for 6 wk (TS), 4) bleomycin instillation plus tobacco smoke exposure for 6 wk (B+TS), and 5) tobacco smoke exposure for 6 wk 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 -smooth muscle actin cells compared with bleomycin alone (B+TS, 3.4 ± 1.2%; TS/B, 3.7 ± 1.5%; B, 2.3 ± 1.5%; P < 0.01). However, only the TS/B group reached a significant increase in lung collagen compared with the 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 an increased number of eosinophils and higher levels of IL-4 and tissue inhibitor of metalloproteinase-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, matrix metalloproteinase-9, and fibroblast proliferation compared with controls, suggesting that tobacco smoke creates a profibrotic milieu that may contribute to the increased bleomycin-induced fibrosis.

matrix metalloproteinase-9; fibroblast proliferation; interleukin-4; tissue inhibitor of metalloproteinase-2; pulmonary fibrosis

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