[en] 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 ultrafine 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 NK(1) and NK(2) receptor antagonist, or a mixture of terfenadine and cimetidine, a histamine H(1) and H(2) 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.
Disciplines :
Veterinary medicine & animal health
Author, co-author :
Nemmar, A.
Delaunois, Annie ; Université de Liège - ULiège > Relations académiques et scientifiques (Méd. vétérinaire)
Nemery, B.
Dessy-Doize, C.
Beckers, Jean-François ; Université de Liège - ULiège > Département de sciences fonctionnelles > Physiologie de la reproduction
Sulon, Joseph ; Université de Liège - ULiège > Département de sciences fonctionnelles > Physiologie de la reproduction
Gustin, Pascal ; Université de Liège - ULiège > Département de sciences fonctionnelles > Pharmacologie, pharmacothérapie et toxicologie
Language :
English
Title :
Inflammatory Effect of Intratracheal Instillation of Ultrafine Particles in the Rabbit: Role of C-Fiber and Mast Cells
Publication date :
01 November 1999
Journal title :
Toxicology and Applied Pharmacology
ISSN :
0041-008X
eISSN :
1096-0333
Publisher :
Academic Press, New York, United States - New York
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