Comparative microarray analysis and pulmonary changes in Brown Norway rats exposed to ovalbumin and concentrated air particulates.
The interaction between air particulates and genetic susceptibility has been implicated in the pathogenesis of asthma. The overall objective of this study was to determine the effects of inhalation exposure to environmentally relevant concentrated air particulates (CAPs) on the lungs of ovalbumin (ova) sensitized and challenged Brown Norway rats. Changes in gene expression were compared with lung tissue histopathology, morphometry, and biochemical and cellular parameters in bronchoalveolar lavage fluid (BALF). Ova challenge was responsible for the preponderance of gene expression changes, related largely to inflammation. CAPs exposure alone resulted in no significant gene expression changes, but CAPs and ova-exposed rodents exhibited an enhanced effect relative to ova alone with differentially expressed genes primarily related to inflammation and airway remodeling. Gene expression data was consistent with the biochemical and cellular analyses of the BALF, the pulmonary pathology, and morphometric changes when comparing the CAPs-ova group to the air-saline or CAPs-saline group. However, the gene expression data were more sensitive than the BALF cell type and number for assessing the effects of CAPs and ova versus the ova challenge alone. In addition, the gene expression results provided some additional insight into the TGF-beta-mediated molecular processes underlying these changes. The broad-based histopathology and functional genomic analyses demonstrate that exposure to CAPs exacerbates rodents with allergic inflammation induced by an allergen and suggests that asthmatics may be at increased risk for air pollution effects.
Heidenfelder
Brooke L
BL
Human Studies Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA.
Reif
David M
DM
Harkema
Jack R
JR
Cohen Hubal
Elaine A
EA
Hudgens
Edward E
EE
Bramble
Lori A
LA
Wagner
James G
JG
Morishita
Masako
M
Keeler
Gerald J
GJ
Edwards
Stephen W
SW
Gallagher
Jane E
JE
D000393:Air Pollutants / Q000633:toxicity*; D000485:Allergens / Q000008:administration & dosage* / Q000276:immunology; D000704:Analysis of Variance; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000276:immunology; D001996:Bronchopneumonia / Q000378:metabolism / Q000473:pathology; D015870:Gene Expression / Q000187:drug effects*; D007249:Inflammation / Q000276:immunology; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D010047:Ovalbumin / Q000008:administration & dosage* / Q000276:immunology; D052638:Particulate Matter / Q000008:administration & dosage / Q000633:toxicity*; D025341:Principal Component Analysis; D051381:Rats; D012130:Respiratory Hypersensitivity / Q000378:metabolism / Q000473:pathology; D020545:Respiratory Mucosa / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology
D000393:Air Pollutants; D000485:Allergens; D052638:Particulate Matter; D010047:Ovalbumin