Intratracheal Instillation of Silica Upregulates Inducible Nitric Oxide Synthase Gene Expression and Increases Nitric Oxide Production in Alveolar Macrophages

Details

• Personal Author:
  Antonini JM ; Blackford JA Jr. ; Castranova, Vincent ; Dey RD
• Description:
  Alveolar macrophages (AM) exposed to cytokines or bacteria) Iipopolysaccharide (LPS) produce the free radical nitric oxide (NO·) by an inducible nitric oxide synthase (iNOS) and release reactive oxygen free radicals following exposure to silica dust. The purpose of the present study was to determine if NO· is produced by rat AM following the intratracheal (IT) instillation of silica, Male Sprague-Dawley rats (175-225 gm) were IT instilled with either silica dust (10 mg/100 gbw) or LPS (0.25 mg/100 gbw). After 24 hr, bronchoalveolar lavage cells (BALC) and lavaged lung tissue were assayed for iNOS mRNA and BALC iNOS-dependent (L-NAME-inhibitable) chemiluminescence and cell counts were also determined. Northern blot analysis demonstrated that the steady-state levels of BALC iNOS mRNA was significantly increased by 3 fold following IT silica and by 7 fold following IT LPS. iNOS-dependent chemiluminescence was significantly increased in AM by 36 fold following IT silica and by 89 fold following IT LPS. Differential counts of BALC showed that AM numbers did not change in any of the treatments, RBC increased by 30 fold following IT silica and by 23 fold following IT LPS. Total leukocytes (polymorphonuclear leukocytes plus lymphocytes) increased by 58 fold following IT silica and by 274 fold following IT LPS. The results demonstrate that BALC iNOS steady-state mRNA levels, AM iNOS-dependent chemiluminescence and total numbers of RBC and leukocytes all increased following IT silica. These findings suggest that NO· production in rat AM is increased in response to silica. NO· has the ability to then combine with superoxide and form a highly reactive, toxic free radical, peroxynitrite that may be responsible for silica-induced lung damage. [Description provided by NIOSH]
• Subjects:
  Animals Environmental Exposure Laboratories Lung Lung Diseases Nitric Oxide Occupational Health Respiratory System Respiratory Tract Diseases Risk Assessment Risk Factors Safety Silicon Dioxide

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• Keywords:
  Bacteria Chemiluminescence Immunoassay Cytokines Exposure Levels Laboratory Animals Lung Disorders Lung Tissue Nitric Oxide Risk Factors Silica Silica Dusts

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• ISSN:
  1073-449X
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  DRDS - Division of Respiratory Disease Studies
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  149
• NIOSHTIC Number:
  nn:20050914
• Citation:
  Am J Respir Crit Care Med 1994 Apr; 149(Abstract Issue):A622
• CAS Registry Number:
  Nitric oxide (CAS RN 10102-43-9) ; Silica (CAS RN 7631-86-9)
• Federal Fiscal Year:
  1994
• Peer Reviewed:
  False
• Source Full Name:
  American Journal of Respiratory and Critical Care Medicine
• Supplement:
  Abstract Issue
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:77578d0bb2c1f330aa632cf96d2a69de83dceb30c3cf195dc04cb5e756b656ed93a27914dbf7d00320898044e0bb6239355af1dd131e8b698cd8f1b94825c305
• Download URL:
  https://stacks.cdc.gov/view/cdc/211096/cdc_211096_DS1.pdf
• File Type:
  [PDF - 584.43 KB ]