Inflammatory effect of intratracheal instillation of ultrafine particles in the rabbit: role of C-fiber and mast cells.
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.
Nemmar
A
A
Faculty of Veterinary Medicine, University of Liège, Liège, B-4000, Belgium.
Delaunois
A
A
Nemery
B
B
Dessy-Doizé
C
C
Beckers
J F
JF
Sulon
J
J
Gustin
P
P
D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D005260:Female; D006632:Histamine / Q000378:metabolism; D006633:Histamine Antagonists / Q000494:pharmacology; D007442:Intubation, Intratracheal; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000648:ultrastructure; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000502:physiology*; D008863:Microspheres; D009412:Nerve Fibers / Q000187:drug effects / Q000502:physiology*; D009504:Neutrophils / Q000502:physiology; D011014:Pneumonia / Q000139:chemically induced* / Q000276:immunology / Q000473:pathology; D011137:Polystyrenes / Q000008:administration & dosage / Q000633:toxicity*; D011817:Rabbits; D018039:Receptors, Tachykinin / Q000037:antagonists & inhibitors; D013373:Substance P / Q000378:metabolism; D015244:Thiorphan / Q000494:pharmacology; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
D006633:Histamine Antagonists; D011137:Polystyrenes; D018039:Receptors, Tachykinin; D013373:Substance P; D003189:p-Methoxy-N-methylphenethylamine; D006632:Histamine; D002217:Carbachol; D015244:Thiorphan; D002211:Capsaicin