ACTIVATED MACROPHAGES AND OZONE TOXICITY

Project Details

Description

Ozone is one of the most ubiquitous and toxic urban air pollutants known.
Exposure to toxic levels of ozone is associated with breakdown of
interstitial collagen and the accumulation of macrophages and neutrophils
(PMN) in the lungs. Although the function of these cells in normal host
defense has been established, their potential role in oxidant induced lung
injury, and their interaction with interstitial connective tissue has not
been elucidated. It is the overall objective of this proposal to examine
the role of interstitial and alveolar macrophages in this process. We
hypothesize that ozone exposure damages lung connective tissue causing the
release of chemotactic collagen fragments. These fragments attract
macrophages and PMN to the lungs. Once localized, these cells become
activated by collagen fragments and macrophage derived factors, and release
mediators that augment the inflammatory response and contribute to
toxicity. In preliminary studies we found that ozone causes breakdown of
lung collagen in vitro. In addition, treatment of rats with ozone (3 ppm)
for 3 hr caused a time dependent accumulation of macrophages in the lungs
which produced elevated levels of hydrogen peroxide and Interleukin-1.
Furthermore, both native and synthetic collagen peptides related to
connective tissue breakdown products induced chemotaxis and stimulated the
release of reactive oxygen mediators from alveolar macrophages. These
results suggest that ozone injured lung interstitium release connective
tissue fragments that attract and activate macrophages. To test our
hypothesis we will analyze the effects of ozone exposure of rats on lung
collagen and macrophage accumulation. We will then characterize the
mechanism underlying the accumulation and activation of macrophages in the
lungs and the potential contribution of these cells to ozone induced
pulmonary injury.
StatusFinished
Effective start/end date1/1/9012/31/20

Funding

  • National Institute of Environmental Health Sciences
  • National Institute of Environmental Health Sciences: $333,594.00
  • National Institute of Environmental Health Sciences: $523,031.00
  • National Institute of Environmental Health Sciences: $293,518.00
  • National Institute of Environmental Health Sciences: $306,283.00
  • National Institute of Environmental Health Sciences: $133,704.00
  • National Institute of Environmental Health Sciences
  • National Institute of Environmental Health Sciences
  • National Institute of Environmental Health Sciences: $589,853.00
  • National Institute of Environmental Health Sciences: $559,543.00
  • National Institute of Environmental Health Sciences
  • National Institute of Environmental Health Sciences
  • National Institute of Environmental Health Sciences: $523,031.00
  • National Institute of Environmental Health Sciences: $336,951.00
  • National Institute of Environmental Health Sciences: $306,283.00
  • National Institute of Environmental Health Sciences: $333,586.00
  • National Institute of Environmental Health Sciences
  • National Institute of Environmental Health Sciences: $36,512.00
  • National Institute of Environmental Health Sciences: $306,283.00
  • National Institute of Environmental Health Sciences: $363,291.00
  • National Institute of Environmental Health Sciences
  • National Institute of Environmental Health Sciences: $156,000.00
  • National Institute of Environmental Health Sciences
  • National Institute of Environmental Health Sciences: $299,085.00
  • National Institute of Environmental Health Sciences
  • National Institute of Environmental Health Sciences: $473,741.00
  • National Institute of Environmental Health Sciences: $341,399.00
  • National Institute of Environmental Health Sciences
  • National Institute of Environmental Health Sciences

ASJC

  • Environmental Science(all)
  • Medicine(all)
  • Cancer Research
  • Pulmonary and Respiratory Medicine

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