Silica Exposure Induces Arginase I Expression in Rat Lung

Details

• Personal Author:
  Castranova, Vincent ; Kepka-Lenhart D ; Mercer RR ; Millecchia L ; Morris SM Jr. ; Poljakovic M ; Porter DW
• Description:
  Induction of arginase (ARG) in some inflammatory lung diseases (e.g., asthma) suggests that it may play a role in bronchoconstriction, fibrosis and airway remodeling by reducing substrate for NO synthesis and enhancing metabolism of arginine to proline and polyamines. Our objectives were to ascertain whether ARG induction is also a feature of silicosis and, if so, to identify the cells expressing type I ARG (ARG I) in rat lung following silica exposure. Sprague-Dawley rats received vehicle or 0.1, 1.0 or 5.0 mg silica/100 g body weight by intratracheal instillation. After 24h, bronchoalveolar lavage (BAL) was performed and markers of pulmonary inflammation, damage and alveolar macrophage (AM) activation were examined. ARG expression was examined by real-time PCR and activity assay. ARG I and iNOS were analyzed by immunohistochemistry. Markers of pulmonary inflammation , damage and AM activation and NO production were significantly increased at all silica doses tested. Silica caused 2- and 3-fold increases in ARG activity at 1 and 5 mg/100 g doses, respectively. ARG I, but not type II ARG, mRNA increased in a similar pattern. In control lungs, ARG I immunoreactivity was observed in AM only. In silica-treated lungs, ARG I immunoreactivity was observed in alveolar type II epithelial cells and in clustered AM, while iNOS was seen only in some AM. ARG activity in AM isolated by BAL also increased significantly after silica treatment. The pattern of ARG I induction is similar to that seen in other models of acute lung disease, suggesting that increases in ARG I may play a common role in the pathology of some lung diseases. Studies to evaluate the impact of inhibiting ARG activity in lung disease are warranted. [Description provided by NIOSH]
• Subjects:
  Aluminum Silicates Animals Asthma Asthma, Occupational Environmental Monitoring Laboratories Lung Diseases Occupational Health Respiratory Tract Diseases Safety Silicon Dioxide

  More +
• Keywords:
  Animal-studies Bronchial-asthma Exposure-assessment Exposure-levels Laboratory-animals Lung-disease Pulmonary-system-disorders Respiratory-system-disorders Silica-dusts Silicates Silicosis

  More +
• ISSN:
  1546-3222
• Document Type:
  Text
• Genre:
  Abstract or Summary ; Proceedings
• Place as Subject:
  OSHA Region 3 ; Pennsylvania ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  2
• NIOSHTIC Number:
  nn:20029005
• Citation:
  Proc Am Thorac Soc 2005 May; 2(Abstracts):A818
• Email:
  mirjana@pitt.edu
• Federal Fiscal Year:
  2005
• Peer Reviewed:
  False
• Source Full Name:
  Proceedings of the American Thoracic Society
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:615b89e53316772acff12e1c9e3115c99ddd911958908500762650aac80e92f4e5a7b4b9379d297e99f1f8e6bfb07d23d4e931f80faac485c72ba13e3b2b7622
• Download URL:
  https://stacks.cdc.gov/view/cdc/190082/cdc_190082_DS1.pdf
• File Type:
  [PDF - 5.83 KB ]