Am. J. Respir. Crit. Care Med., Volume 164, Number 8, October 2001, 1438-1443

Ambient Urban Baltimore Particulate-induced Airway Hyperresponsiveness and Inflammation in Mice

DIANNE M. WALTERS, PATRICK N. BREYSSE, and MARSHA WILLS-KARP

The Johns Hopkins School of Hygiene and Public Health, Department of Environmental Health Sciences, Baltimore, Maryland; and Children's Hospital Medical Center, Division of Immunobiology, Cincinnati, Ohio

Airborne particulate matter (PM) is hypothesized to play a role in increases in asthma prevalence, although a causal relationship has yet to be established. To investigate the effects of real-world PM exposure on airway reactivity (AHR) and bronchoalveolar lavage (BAL) cellularity, we exposed naive mice to a single dose (0.5 mg/ mouse) of ambient PM, coal fly ash, or diesel PM. We found that ambient PM exposure induced increases in AHR and BAL cellularity, whereas diesel PM induced significant increases in BAL cellularity, but not AHR. On the other hand, coal fly ash exposure did not elicit significant changes in either of these parameters. We further examined ambient PM-induced temporal changes in AHR, BAL cells, and lung cytokine levels over a 2-wk period. Ambient PM-induced AHR was sustained over 7 d. The increase in AHR was preceded by dramatic increases in BAL eosinophils, whereas a decline in AHR was associated with increases in macrophages. A Th2 cytokine pattern (IL-5, IL-13, eotaxin) was observed early on with a shift toward a Th1 pattern (IFN-). In additional studies, we found that the active component(s) of ambient PM are not water-soluble and that ambient PM-induced AHR and inflammation are dose- dependent. We conclude that ambient PM can induce asthmalike parameters in naive mice, suggesting that PM exposure may be an important factor in increases in asthma prevalence.

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