TY - JOUR
T1 - Inflammatory effect of intratracheal instillation of ultrafine particles in the rabbit
T2 - Role of C-fiber and mast cells
AU - Nemmar, A.
AU - Delaunois, A.
AU - Nemery, B.
AU - Dessy-Doizé, C.
AU - Beckers, J. F.
AU - Sulon, J.
AU - Gustin, Pascal
N1 - Funding Information:
The authors thank Dr Edmonds-Alt (Sanofi Recherche, Montpellier, France) for his kind provision of SR 140333 and SR 48968. This work was supported by the Special Research Funds of the University of Liège.
PY - 1999/11/1
Y1 - 1999/11/1
N2 - 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.
AB - 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.
KW - C-fibers
KW - Histamine
KW - Lung
KW - Mast cells
KW - Neutrophils
KW - Rabbit
KW - Substance P
KW - Ultrafine particles
UR - http://www.scopus.com/inward/record.url?scp=0033229884&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033229884&partnerID=8YFLogxK
U2 - 10.1006/taap.1999.8762
DO - 10.1006/taap.1999.8762
M3 - Article
C2 - 10544059
AN - SCOPUS:0033229884
SN - 0041-008X
VL - 160
SP - 250
EP - 261
JO - Toxicology and Applied Pharmacology
JF - Toxicology and Applied Pharmacology
IS - 3
ER -