Particulate matter in cigarette smoke alters iron homeostasis to produce a biological effect.
BACKGROUND
Lung injury after cigarette smoking is related to particle retention. Iron accumulates with the deposition of these particles.


OBJECTIVE
We tested the postulate that (1) injury after smoking correlates with exposure to the particulate fraction of cigarette smoke, (2) these particles alter iron homeostasis, triggering metal accumulation, and (3) this alteration in iron homeostasis affects oxidative stress and inflammation.


METHODS
Rats and human respiratory epithelial cells were exposed to cigarette smoke, filtered cigarette smoke, and cigarette smoke condensate (the particulate fraction of smoke), and indices of iron homeostasis, oxidative stress, and inflammatory injury were determined. Comparable measures were also evaluated in nonsmokers and smokers.


RESULTS
After exposure of rats to cigarette smoke, increased lavage concentrations of iron and ferritin, serum ferritin levels, and nonheme iron concentrations in the lung and liver tissue all increased. Lavage ascorbate concentrations were decreased, supporting an oxidative stress. After filtering of the cigarette smoke to remove particles, most of these changes were reversed. Exposure of cultured respiratory epithelial cells to cigarette smoke condensate caused a similar accumulation of iron, metal-dependent oxidative stress, and increased IL-8 release. Lavage samples in healthy smokers and smoking patients with chronic obstructive pulmonary disease revealed elevated concentrations of both iron and ferritin relative to healthy nonsmokers. Lavage ascorbate decreased with cigarette smoking. Serum iron and ferritin levels among smokers were increased, supporting systemic accumulation of this metal after cigarette smoke exposure.


CONCLUSIONS
We conclude that cigarette smoke particles alter iron homeostasis, both in the lung and systemically.
Ghio
Andrew J
AJ
National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA. ghio.andy@epa.gov
Hilborn
Elizabeth D
ED
Stonehuerner
Jacqueline G
JG
Dailey
Lisa A
LA
Carter
Jacqueline D
JD
Richards
Judy H
JH
Crissman
Kay M
KM
Foronjy
Robert F
RF
Uyeminami
Dale L
DL
Pinkerton
Kent E
KE
D000293:Adolescent; D000328:Adult; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D016022:Case-Control Studies; D004195:Disease Models, Animal; D005260:Female; D006706:Homeostasis; D006801:Humans; D007249:Inflammation / Q000209:etiology; D007501:Iron / Q000378:metabolism*; D055370:Lung Injury / Q000150:complications / Q000209:etiology* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D052638:Particulate Matter / Q000009:adverse effects*; D051381:Rats; D017208:Rats, Wistar; D012737:Sex Factors; D012907:Smoking / Q000009:adverse effects*; D055815:Young Adult
D052638:Particulate Matter; D007501:Iron