Inflammatory effect of intratracheal instillation of ultrafine particles in the rabbit: Role of C-fiber and mast cells

A. Nemmar, A. Delaunois, B. Nemery, C. Dessy-Doizé, J. F. Beckers, J. Sulon, Pascal Gustin

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50 Citations (Scopus)


The effects of ultrafine polystyrene carboxylate-modified (fluorospheres) on inflammatory processes are being investigated in rabbit lungs. One milliliter of sterile NaCl (0.9%) containing 4 mg of ultra fine particles (UFP) was intratracheally instilled into anesthetized rabbits. The control animals were only instilled with sterile NaCl (0.9%). Twenty hours after being instilled, the rabbits were killed and their lungs were excised and then tracheally perfused with phosphate-buffered physiological solution (PBS). The lung effluents, collected from small holes made in the pleura, were analyzed for substance P (SP) and histamine content by radioimmunoassay (RIA) methods, after administration of drugs. In addition, in other groups of rabbits, the lung wet/dry (W/D) weight ratio was monitored, as were the cellular and protein contents in bronchoalveolar lavage (BAL). Electron microscopy examination was also performed. In tracheally superfused experiments, UFP induced a significant enhancement of both SP and histamine releases after administration of capsaicin (10-4 M), to stimulate C-fiber, and carbachol (10-4 M), a cholinergic agonist. A significant increase in histamine release was also recorded in the UFP-instilled group following the administration of both SP (10-6 M) plus thiorphan (10-5 M) and compound 48/80 (C48/80) (10-3 M) to stimulate mast cells. In addition, the BAL fluid analysis of UFP groups showed an influx of neutrophils and an increase in total protein concentration. An increase in the lung WW/DW ratio was also recorded. Both epithelial and endothelial injuries were observed in the lungs of UFP-instilled rabbits. The pretreatment of rabbits in vivo with a mixture of either SR 140333 and SR 48368, a tachykinin NK1 and NK2 receptor antagonist, or a mixture of terfenadine and cimetidine, a histamine H1 and H2 receptor antagonist, prevented UFP- induced neutrophil influx and increased total proteins and lung WW/DW ratio. Therefore, it can be concluded that chemicaly inert, electrically charged UFP induce a pulmonary inflammatory process during which the release of SP and histamine from C- fibers and mast cells was enhanced after various stimuli. These latter mediators can also modulate the inflammatory process.

Original languageEnglish
Pages (from-to)250-261
Number of pages12
JournalToxicology and Applied Pharmacology
Issue number3
Publication statusPublished - Nov 1 1999
Externally publishedYes


  • C-fibers
  • Histamine
  • Lung
  • Mast cells
  • Neutrophils
  • Rabbit
  • Substance P
  • Ultrafine particles

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology


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