Concordance Between In Vitro and In Vivo Dosimetry in the Proinflammatory Effects of Low-Toxicity, Low-Solubility Particles: The Key Role of the Proximal Alveolar Region

Details

• Personal Author:
  Borm PJA ; Donaldson K ; Oberdorster G ; Pinkerton KE ; Stone V ; Tran CL
• Description:
  We previously demonstrated the importance of the surface area burden as the key dose metric in the elicitation of inflammation in rat lungs by low-solubility, low-toxicity particles (LSLTP). We have now explored the dosimetry of LSLTP in vitro using epithelial cell interleukin (IL)-8 gene expression as a surrogate for potential of particles to cause inflammation. The proximal alveolar region (PAR) of the lung has been identified as a key site for the retention of respirable particles, as it receives high deposition but has slow clearance compared to the larger airways. For these reasons, a few days after exposure to particles the residual dose is concentrated in the PAR region. Re-expressing our rat lung data as particle surface area burden per unit of PAR surface area we obtained a threshold value for onset of inflammation of 1 cm(2)/cm(2). We carried out dose responses in vitro for onset of IL-8 gene expression with the same particles as we had used in vivo. When we expressed the in vitro dose as surface area dose per unit A549cell culture surface area, we obtained a threshold of 1 cm(2)/cm(2). This concordance between proinflammatory effects in vivo (PMN in BAL) and in vitro (epithelial IL-8 gene expression) confirms and supports the utility of the particle surface area metric and the importance of the PAR. These studies also open the way for future in vitro approaches to studying proinflammatory effects of a range of toxic particles based on sound dosimetry that complements animal use in particle toxicology. [Description provided by NIOSH]
• Subjects:
  Immune System Laboratories Lung Occupational Health Particulate Matter Radiation Dosimeters Respiratory System Safety Toxicology
• Keywords:
  Cell Biology Dosimetry Gene Expression Immune Reaction In Vitro Studies In Vivo Studies Laboratory Animals Lung Cells Lung Irritants Particulates Toxicopathology

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• ISSN:
  0895-8378
• Document Type:
  Text
• Funding:
  Cooperative Agreement
• Genre:
  Journal Article
• Place as Subject:
  California ; OSHA Region 9
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  53-62
• Volume:
  20
• Issue:
  1
• NIOSHTIC Number:
  nn:20033231
• Citation:
  Inhal Toxicol 2008 Jan; 20(1):53-62
• Contact Point Address:
  K. Donaldson, MRC/University of Edinburgh Centre for Inflammation Research, ELEGI Colt Laboratory, Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh, EH16 4TJ, UK
• Email:
  ken.donaldson@ed.ac.uk
• Federal Fiscal Year:
  2008
• NORA Priority Area:
  Agriculture, Forestry and Fishing
• Performing Organization:
  University of California - Davis
• Peer Reviewed:
  True
• Start Date:
  20010930
• Source Full Name:
  Inhalation Toxicology
• End Date:
  20270929
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:461206e60c67310fdd7fbc4b8645faa1a5141d7f939032eae764157c839a8162a0e7b0cd6c1236a437c0a54f2fa5bbae51c2b3e8b7aa74ea1a782586ace5a41b
• Download URL:
  https://stacks.cdc.gov/view/cdc/188884/cdc_188884_DS1.pdf
• File Type:
  [PDF - 4.10 MB ]