Emphysematous lung destruction by cigarette smoke. The effects of latent adenoviral infection on the lung inflammatory response.
This study was designed to test the hypothesis that cigarette smoke-induced inflammation and emphysema are amplified by the presence of latent adenoviral (Ad) infection, and to determine whether this emphysematous process can be reversed by all-trans-retinoic acid (RA) treatment. The results confirm that in guinea pigs, chronic cigarette-smoke exposure caused lesions similar to human centrilobular emphysema. They also show that latent Ad infection combined with cigarette-smoke exposure caused an excess increase in lung volume (P < 0.001), air-space volume (P < 0.001), and lung weight (P < 0.01), and further decrease in surface-to-volume ratio (P < 0.001) compared with smoke exposure alone. RA treatment failed to reverse these emphysematous changes. Analysis of inflammatory response in parenchymal and airway tissue showed that smoking caused an increase of polymorphonuclear leukocytes (PMNs) (P < 0.0002), macrophages (P < 0.001), and CD4 cells (P < 0.0009), and that latent Ad infection independently increased PMNs (P < 0.001), macrophages (P = 0.003), and CD8 cells (P < 0.001). We conclude that latent Ad infection amplifies the emphysematous lung destruction and increases the inflammatory response produced by cigarette-smoke exposure. In this study, the increase in CD4 was associated with cigarette smoke and the increase in CD8 cells with latent Ad infection.
Meshi
Bernard
B
UBC McDonald Research Laboratories, The iCAPTURE Center, St. Paul's Hospital, Vancouver, British Columbia, Canada.
Vitalis
Timothy Z
TZ
Ionescu
Diana
D
Elliott
W Mark
WM
Liu
Chun
C
Wang
Xiang-Dong
XD
Hayashi
Shizu
S
Hogg
James C
JC
D000256:Adenoviridae / Q000235:genetics*; D000704:Analysis of Variance; D000818:Animals; D001835:Body Weight; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004646:Emphysema / Q000139:chemically induced*; D005260:Female; D006168:Guinea Pigs; D007249:Inflammation; D008168:Lung / Q000276:immunology / Q000473:pathology* / Q000821:virology*; D008264:Macrophages / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism; D009929:Organ Size; D012907:Smoking; D014212:Tretinoin / Q000097:blood / Q000494:pharmacology
D014212:Tretinoin