Silica-induced oxygen radical generation in alveolar macrophage

Ind Health. 1997 Jul;35(3):380-7. doi: 10.2486/indhealth.35.380.


Silica is a well-known occupational fibrogenic agent and its primary target cell is alveolar macrophage. Particle-stimulated macrophages are believed to release various mediator which can regulate the inflammation as well as pulmonary fibrosis. Even though oxygen radicals play the major role among these mediators, the mechanisms concerning the stimulation of alveolar macrophages are not clear yet. The present study was carried out to investigate the signal transduction pathway on oxygen radical generation in silica-stimulated alveolar macrophages. Silica induced oxygen radical generation in a dose-response pattern. Extracellular calcium depletion, calcium channel blockers, and calcium release blocker decreased the effect of silica on oxygen radical generation. Silica increased intracellular calcium through the influx of calcium through the calcium channel and the calcium release from the intracellular calcium store. To know the role of protein kinase C (PKC), phospholipase C (PLC), and protein tyrosine kinase (PTK) in silica-induced oxygen radical generation, we pretreated alveolar macrophages with inhibitors of these enzymes. Inhibitors of PKC (sphingosine and staurosporine), PLC (neomycin and U-73122), and PTK (genistein and erbstatin) suppressed the silica-induced oxygen radical generation. Silica increased the PLC activity at the concentration of 5 mg/ml. The inhibitors of PTK and PLC suppressed the action of silica on the PLC activity. From these results, we suggest that silica induces oxygen radical generation through PTK, PLC, and PKC in alveolar macrophages.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism
  • Dose-Response Relationship, Drug
  • Enzyme Activation
  • Free Radicals / metabolism
  • Luminescent Measurements
  • Macrophages, Alveolar / drug effects
  • Macrophages, Alveolar / metabolism*
  • Male
  • Protein Kinase C / metabolism
  • Protein-Tyrosine Kinases / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Reactive Oxygen Species / metabolism*
  • Silicon Dioxide / adverse effects*
  • Spectrometry, Fluorescence
  • Type C Phospholipases / metabolism


  • Free Radicals
  • Reactive Oxygen Species
  • Silicon Dioxide
  • Protein-Tyrosine Kinases
  • Protein Kinase C
  • Type C Phospholipases
  • Calcium