Abstract
Coarse and fine particulate matter (PM2.5-10 and PM2.5, respectively) are regulated ambient air pollutants thought to have major adverse health effects in exposed humans. The role of endotoxin and other bioaerosol components in the toxicity of PM from ambient air is controversial. This study evaluated the inflammatory lung response in mice instilled intratracheally with PM2.5-10 and PM2.5 emitted from a working dairy barn, a source presumed to have elevated concentrations of endotoxin. PM2.5-10 was more pro-inflammatory on an equal weight basis than was PM2.5; both fractions elicited a predominantly neutrophilic response. The inflammatory response was reversible, with a peak response to PM2.5-10 observed at 24 h after instillation, and a return to control values by 72 h after instillation. The major active pro-inflammatory component in whole PM2.5-10, but not in whole PM2.5, is heat-labile, consistent with it being endotoxin. A heat treatment protocol for the gradual inactivation of biological materials in the PM fractions over a measurable time course was developed and optimized in this study using pure lipopolysaccharide (LPS) as a model system. The time course of heat inactivation of pure LPS and of endotoxin activity in PM2.5-10 as measured by Limulus bioassay is identical. The active material in both PM2.5-10 and PM2.5 remained in the insoluble fraction when the whole PM samples were extracted with physiological saline solution. Histological analysis of lung sections from mice instilled with PM2.5-10 or PM2.5 showed evidence of inflammation consistent with the cellular responses observed in lung lavage fluid. The major pro-inflammatory components present in endotoxin-rich PM were found in the insoluble fraction of PM2.5-10; however, in contrast with PM2.5-10 isolated from ambient air in the Central Valley of California, the active components in the insoluble fraction were heat-labile.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 348-357 |
| Number of pages | 10 |
| Journal | Toxicology and Applied Pharmacology |
| Volume | 236 |
| Issue number | 3 |
| DOIs | |
| State | Published - May 1 2009 |
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Keywords
- Air pollution
- Bronchoalveolar lavage
- Coarse PM (PM)
- Endotoxin
- Fine PM (PM)
ASJC Scopus subject areas
- Pharmacology
- Toxicology
Cite this
Mouse lung inflammation after instillation of particulate matter collected from a working dairy barn. / Wegesser, Teresa C.; Last, Jerold A.
In: Toxicology and Applied Pharmacology, Vol. 236, No. 3, 01.05.2009, p. 348-357.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Mouse lung inflammation after instillation of particulate matter collected from a working dairy barn
AU - Wegesser, Teresa C.
AU - Last, Jerold A
PY - 2009/5/1
Y1 - 2009/5/1
N2 - Coarse and fine particulate matter (PM2.5-10 and PM2.5, respectively) are regulated ambient air pollutants thought to have major adverse health effects in exposed humans. The role of endotoxin and other bioaerosol components in the toxicity of PM from ambient air is controversial. This study evaluated the inflammatory lung response in mice instilled intratracheally with PM2.5-10 and PM2.5 emitted from a working dairy barn, a source presumed to have elevated concentrations of endotoxin. PM2.5-10 was more pro-inflammatory on an equal weight basis than was PM2.5; both fractions elicited a predominantly neutrophilic response. The inflammatory response was reversible, with a peak response to PM2.5-10 observed at 24 h after instillation, and a return to control values by 72 h after instillation. The major active pro-inflammatory component in whole PM2.5-10, but not in whole PM2.5, is heat-labile, consistent with it being endotoxin. A heat treatment protocol for the gradual inactivation of biological materials in the PM fractions over a measurable time course was developed and optimized in this study using pure lipopolysaccharide (LPS) as a model system. The time course of heat inactivation of pure LPS and of endotoxin activity in PM2.5-10 as measured by Limulus bioassay is identical. The active material in both PM2.5-10 and PM2.5 remained in the insoluble fraction when the whole PM samples were extracted with physiological saline solution. Histological analysis of lung sections from mice instilled with PM2.5-10 or PM2.5 showed evidence of inflammation consistent with the cellular responses observed in lung lavage fluid. The major pro-inflammatory components present in endotoxin-rich PM were found in the insoluble fraction of PM2.5-10; however, in contrast with PM2.5-10 isolated from ambient air in the Central Valley of California, the active components in the insoluble fraction were heat-labile.
AB - Coarse and fine particulate matter (PM2.5-10 and PM2.5, respectively) are regulated ambient air pollutants thought to have major adverse health effects in exposed humans. The role of endotoxin and other bioaerosol components in the toxicity of PM from ambient air is controversial. This study evaluated the inflammatory lung response in mice instilled intratracheally with PM2.5-10 and PM2.5 emitted from a working dairy barn, a source presumed to have elevated concentrations of endotoxin. PM2.5-10 was more pro-inflammatory on an equal weight basis than was PM2.5; both fractions elicited a predominantly neutrophilic response. The inflammatory response was reversible, with a peak response to PM2.5-10 observed at 24 h after instillation, and a return to control values by 72 h after instillation. The major active pro-inflammatory component in whole PM2.5-10, but not in whole PM2.5, is heat-labile, consistent with it being endotoxin. A heat treatment protocol for the gradual inactivation of biological materials in the PM fractions over a measurable time course was developed and optimized in this study using pure lipopolysaccharide (LPS) as a model system. The time course of heat inactivation of pure LPS and of endotoxin activity in PM2.5-10 as measured by Limulus bioassay is identical. The active material in both PM2.5-10 and PM2.5 remained in the insoluble fraction when the whole PM samples were extracted with physiological saline solution. Histological analysis of lung sections from mice instilled with PM2.5-10 or PM2.5 showed evidence of inflammation consistent with the cellular responses observed in lung lavage fluid. The major pro-inflammatory components present in endotoxin-rich PM were found in the insoluble fraction of PM2.5-10; however, in contrast with PM2.5-10 isolated from ambient air in the Central Valley of California, the active components in the insoluble fraction were heat-labile.
KW - Air pollution
KW - Bronchoalveolar lavage
KW - Coarse PM (PM)
KW - Endotoxin
KW - Fine PM (PM)
UR - http://www.scopus.com/inward/record.url?scp=63649129512&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=63649129512&partnerID=8YFLogxK
U2 - 10.1016/j.taap.2009.02.023
DO - 10.1016/j.taap.2009.02.023
M3 - Article
VL - 236
SP - 348
EP - 357
JO - Toxicology and Applied Pharmacology
JF - Toxicology and Applied Pharmacology
SN - 0041-008X
IS - 3
ER -