Inflammatory time course after quartz instillation: role of tumor necrosis factor-alpha and particle surface.
Inflammation has been suggested as the key factor in the development of quartz-induced fibrosis and carcinogenesis, and particle surface properties are argued as an important characteristic responsible for these pathologic alterations. To evaluate the effect of surface modification on acute and subchronic inflammation, female Wistar rats were intratracheally instilled with 2 mg native quartz, or quartz coated either with polyvinyl-pyridine-N-oxide or with aluminium lactate. Various markers of lung toxicity, inflammation, and oxidative stress were found to be enhanced at 3, 7, 21, and 90 d after instillation of native quartz. Quartz-treated animals also showed enhanced immunostaining of nuclear factor-kappaB (NF-kappaB) in alveolar macrophages and lung epithelium, as well as reduced IkappaBalpha levels in whole lung homogenate. Both surface modifications were found to inhibit most of the effects as observed with native quartz. NF-kappaB activation was also observed in vitro in rat lung epithelial cells following treatment with lavage fluid from quartz-treated animals, as well as with conditioned medium of quartz-treated macrophages, and these effects appeared to be at least partly tumor necrosis factor-alpha-independent. In conclusion, the persistent subchronic inflammatory lung response after quartz exposure appears to be particle surface-driven and is associated with NF-kappaB activation in both alveolar macrophages and the lung epithelium.
Albrecht
Catrin
C
Institut für Umweltmedizinische Forschung (IUF), Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany. catrin.albrecht@uni-duesseldorf.de
Schins
Roel P F
RP
Höhr
Doris
D
Becker
Andrea
A
Shi
Tingming
T
Knaapen
Ad M
AM
Borm
Paul J A
PJ
D000818:Animals; D002273:Carcinogens / Q000009:adverse effects*; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D011014:Pneumonia / Q000139:chemically induced / Q000276:immunology / Q000473:pathology; D011791:Quartz / Q000009:adverse effects*; D051381:Rats; D017208:Rats, Wistar; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013499:Surface Properties; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism*
D002273:Carcinogens; D017077:Culture Media, Conditioned; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D011791:Quartz