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) o n inflammatory processes are being investigated in rabbit lungs. One millil iter of sterile NaCl (0.9%) containing 4 mg of ultrafine particles (UFP) wa s intratracheally instilled into anesthetized rabbits. The control animals were only instilled with sterile NaCl (0.9%), Twenty hours after being inst illed, the rabbits were killed and their lungs were excised and then trache ally perfused with phosphate-buffered physiological solution (PBS), The lun g effluents, collected from small holes made in the pleura, were analyzed f or substance P (SP) and histamine content by radioimmunoassay (RIA) methods , after administration of drugs. In addition, in other groups of rabbits, t he lung wet/dry (W/D) weight ratio was monitored, as were the cellular and protein contents in bronchoalveolar lavage (BAL). Electron microscopy exami nation was also performed. In tracheally superfused experiments, UFP induce d a significant enhancement of both SP and histamine releases after adminis tration of capsaicin (10(-4) M), to stimulate C-fiber, and carbachol (10(-4 ) M), a cholinergic agonist. A significant increase in histamine release wa s also recorded in the UFP-instilled group following the administration of both SP (10(-6) hi) plus thiorphan (10(-5) M) and compound 48/80 (C48/80) ( 10(-3) hi) 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-inst illed 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 H-1 and H-2 receptor an tagonist, prevented UFP- induced neutrophil influx and increased total prot eins and lung WW/DW ratio. Therefore, it can be concluded that chemicaly in ert, electrically charged UFP induce a pulmonary inflammatory process durin g which the release of SP and histamine from C-fibers and mast cells was en hanced after various stimuli. These latter mediators can also modulate the inflammatory process. (C) 1999 Academic Press.