Different lung responses to cigarette smoke in two strains of mice sensitive to oxidants.
The development of cigarette smoke-induced pulmonary changes in C57 Bl/6J and DBA/2 mice was investigated. Both strains are sensitive to oxidants and C57Bl/6J mice are moderately deficient in serum alpha1-proteinase inhibitor. Following chronic exposure to cigarette smoke, patchy emphysema was present in mice of both strains, but developed faster in DBA/2 mice. A positive reaction for mouse neutrophil elastase was seen on the septa of both strains. Additionally, the DBA/2 mice developed a uniform parenchymal dilation that was preceded by the appearance of apoptotic cells in areas with a low signal for vascular endothelial growth factor-receptor 2. Fibrotic areas scattered throughout the parenchyma, coupled with a positive immunohistochemical reaction for transforming growth factor-beta was seen only in DBA/2 mice. Both DBA/2 and C57Bl/6J strains showed epithelial cell injury and areas of deciliation in their airways. However, the appearance of goblet cell metaplasia was common in C57Bl/6J mice but rare in DBA/2 mice. A positive immunohistochemical reaction for interleukin (IL)-4, IL-13 and MUC5AC was seen only in the airways of C57Bl/6J mice. Strain characteristics (alpha1-proteinase inhibitor levels, sensitivity to oxidants, and constitutive levels of vascular endothelial growth factor-receptor 2) and phenotypical responses (apoptosis and cytokine distribution) may condition parenchymal and airway changes to cigarette smoke.
Bartalesi
B
B
Dipartimento di Fisiopatologia e Medicina Sperimentale, Università di Siena, Via Aldo Moro n.6, I-53100 Siena, Italy.
Cavarra
E
E
Fineschi
S
S
Lucattelli
M
M
Lunghi
B
B
Martorana
P A
PA
Lungarella
G
G
D000704:Analysis of Variance; D000818:Animals; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008853:Microscopy / Q000379:methods; D016877:Oxidants / Q000494:pharmacology*; D011336:Probability; D011656:Pulmonary Emphysema / Q000000981:diagnostic imaging* / Q000473:pathology*; D012307:Risk Factors; D012720:Severity of Illness Index; D013045:Species Specificity; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*; D014463:Ultrasonography
D016877:Oxidants; D014028:Tobacco Smoke Pollution