Cigarette smoke exposure potentiates bleomycin-induced lung fibrosis in guinea pigs.
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 alpha-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.
Cisneros-Lira
José
J
Facultad de Ciencias, UNAM, Apartado Postal 21-630, Coyoacan México DF, 04000, Mexico.
Gaxiola
Miguel
M
Ramos
Carlos
C
Selman
Moisés
M
Pardo
Annie
A
D000199:Actins / Q000378:metabolism; D000818:Animals; D001761:Bleomycin; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002455:Cell Division; D004781:Environmental Exposure; D005347:Fibroblasts / Q000473:pathology; D006168:Guinea Pigs; D006909:Hydroxyproline / Q000378:metabolism; D007375:Interleukin-1 / Q000032:analysis; D008168:Lung / Q000378:metabolism / Q000473:pathology; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009130:Muscle, Smooth / Q000378:metabolism / Q000473:pathology; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000473:pathology*; D012906:Smoke / Q000009:adverse effects*; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000032:analysis; D014026:Nicotiana
D000199:Actins; D007375:Interleukin-1; D012906:Smoke; D001761:Bleomycin; D019716:Tissue Inhibitor of Metalloproteinase-2; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D006909:Hydroxyproline