Extracellular cadmium in the bronchoalveolar space of long-term tobacco smokers with and without COPD and its association with inflammation.
Tobacco contains cadmium, and this metal has been attributed a causative role in pulmonary emphysema among smokers, although extracellular cadmium has not to date been quantified in the bronchoalveolar space of tobacco smokers with or without COPD. We determined whether cadmium is enhanced in the bronchoalveolar space of long-term tobacco smokers with or without COPD in vivo, its association with inflammation, and its effect on chemokine release in macrophage-like cells in vitro. Bronchoalveolar lavage (BAL), sputum, and blood samples were collected from current, long-term smokers with and without COPD and from healthy nonsmokers. Cadmium concentrations were determined in cell-free BAL fluid using inductively coupled plasma mass spectrometry. Blood monocyte-derived macrophages were exposed to cadmium chloride in vitro. Depending upon the type of sample, molecular markers of inflammation were quantified either as protein (enzyme-linked immunosorbent assay) or as mRNA (real-time polymerase chain reaction). Cadmium concentrations were markedly increased in cell-free BAL fluid of smokers compared to that of nonsmokers (n=19-29; P<0.001), irrespective of COPD. In these smokers, the measured cadmium displayed positive correlations with macrophage TNF-α mRNA in BAL, neutrophil and CD8(+) cell concentrations in blood, and finally with IL-6, IL-8, and MMP-9 protein in sputum (n=10-20; P<0.05). The cadmium chloride exposure caused a concentration-dependent increase in extracellular IL-8 protein in monocyte-derived macrophages in vitro. In conclusion, extracellular cadmium is enhanced in the bronchoalveolar space of long-term smokers and displays pro-inflammatory features. Its pathogenic role in tobacco-induced disease deserves further evaluation.
Unit for Lung and Airway Research, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Britt-Marie
BM
Sundblad
Unit for Lung and Airway Research, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Jie
J
Ji
Unit for Lung and Airway Research, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Bettina
B
Levänen
Unit for Occupational and Environmental Dermatology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Klara
K
Midander
Unit for Occupational and Environmental Dermatology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Anneli
A
Julander
Unit for Lung and Airway Research, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Kjell
K
Larsson
Unit for Lung and Airway Research, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Lena
L
Palmberg
Unit for Lung and Airway Research, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Anders
A
Lindén
D000328:Adult; D000368:Aged; D001980:Bronchi / Q000737:chemistry*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002104:Cadmium / Q000032:analysis*; D005110:Extracellular Space / Q000737:chemistry*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000150:complications*; D008297:Male; D008875:Middle Aged; D011650:Pulmonary Alveoli / Q000737:chemistry*; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications*; D012907:Smoking / Q000009:adverse effects*; D013183:Sputum / Q000737:chemistry; D055815:Young Adult
D002104:Cadmium
cigarette; macrophage; metal; neutrophil; obstruction