Age specific responses to acute inhalation of diffusion flame soot particles: cellular injury and the airway antioxidant response.
Current studies of particulate matter (PM) are confounded by the fact that PM is a complex mixture of primary (crustal material, soot, metals) and secondary (nitrates, sulfates, and organics formed in the atmosphere) compounds with considerable variance in composition by sources and location. We have developed a laboratory-based PM that is replicable, does not contain dust or metals and that can be used to study specific health effects of PM composition in animal models. We exposed both neonatal (7 days of age) and adult rats to a single 6-h exposure of laboratory generated fine diffusion flame particles (DFP; 170 µg/m(3)), or filtered air. Pulmonary gene and protein expression as well as indicators of cytotoxicity were evaluated 24 h after exposure. Although DFP exposure did not alter airway epithelial cell composition in either neonates or adults, increased lactate dehydrogenase activity was found in the bronchoalveolar lavage fluid of neonates indicating an age-specific increase in susceptibility. In adults, 16 genes were differentially expressed as a result of DFP exposure whereas only 6 genes were altered in the airways of neonates. Glutamate cysteine ligase protein was increased in abundance in both DFP exposed neonates and adults indicating an initiation of antioxidant responses involving the synthesis of glutathione. DFP significantly decreased catalase gene expression in adult airways, although catalase protein expression was increased by DFP in both neonates and adults. We conclude that key airway antioxidant enzymes undergo changes in expression in response to a moderate PM exposure that does not cause frank epithelial injury and that neonates have a different response pattern than adults.
Van Winkle
Laura S
LS
Department of Anatomy, Physiology and Cell Biology, School of Veterinary Medicine, University of California Davis, Davis, California 95616-8732, USA. lsvanwinkle@ucdavis.edu
Chan
Jackie K W
JK
Anderson
Donald S
DS
Kumfer
Benjamin M
BM
Kennedy
Ian M
IM
Wexler
Anthony S
AS
Wallis
Christopher
C
Abid
Aamir D
AD
Sutherland
Katherine M
KM
Fanucchi
Michelle V
MV
D000280:Administration, Inhalation; D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D000975:Antioxidants / Q000378:metabolism*; D001992:Bronchoalveolar Lavage Fluid; D002374:Catalase / Q000378:metabolism; D015870:Gene Expression; D005721:Glutamate-Cysteine Ligase / Q000378:metabolism; D001239:Inhalation; D008168:Lung / Q000473:pathology*; D008297:Male; D010316:Particle Size; D052638:Particulate Matter / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012137:Respiratory System / Q000378:metabolism / Q000473:pathology*; D053260:Soot / Q000633:toxicity*
D000975:Antioxidants; D052638:Particulate Matter; D053260:Soot; D002374:Catalase; D005721:Glutamate-Cysteine Ligase