Toluene Diisocyanate Enhances Substance P in Sensory Neurons Innervating the Nasal Mucosa

Abstract

Inhalation of irritants, such as toluene diisocyanate (TDI), stimulates substance P (SP) release from peripheral processes of sensory neurons innervating the airways. The purpose of this study was to determine if TDI inhalation affects intraneuronal levels of SP and preprotachykinin (PPT) messenger RNA (mRNA) in the sensory neurons of the trigeminal ganglion (TG) which innervate the nasal epithelium. The nasal cavity of Fisher-344 rats was instilled with rhodamine-labeled latex microspheres. Ten days later, the rats were exposed to 60 ppb of 2,4-2,6-TDI vapor for 2 h. The TG were removed 1, 12, 24, 48, 72, and 96 h after TDI treatment and prepared for SP immunocytochemistry and PPT in situ hybridization. SP nerve fiber density in nasal epithelium was significantly increased 12, 24, and 48 h after TDI exposure. The proportion of microsphere-labeled cell bodies expressing high levels of SP immunoreactivity was decreased at 24 h but was increased above controls at 48 and 72 h. The proportion of microsphere-labeled cell bodies expressing high levels of PPT mRNA was increased above control levels at 24 and 48 h. The percentage of leukocytes observed in nasal lavage fluid was significantly increased 12, 24, 48, and 72 h after inhalation. These studies indicate that SP production in TG neurons projecting to the nasal epithelium is transiently increased after TDI exposure, suggesting that TDI inhalation not only causes SP release but also increased intraneuronal neuropeptide levels. Increased neuronal SP levels may be involved in maintaining neurogenic inflammation or the development of airway hyperresponsiveness.

Toxic Rhinitis-Induced Changes of Human Nasal Mucosa Innervation

“…After TDI exposure of rats, SP-immunoreactive nerve fiber density was significantly increased in nasal epithelium. Also, the proportion of microsphere-labeled cell bodies expressing high levels of SP-immunoreactivity was increased at 48 and 72 hours after TDI exposure (15). The present study demonstrated a similar tendency in increase of SP expression in mucosal nerve fibers of human toxic rhinitis and indicates similarities in the pathophysiology of these two irritants.…”

“…Recently, a study was carried out to investigate the effects of environmental irritants on nasal mucosa innervation using an animal model and toluene diisocyanate (TDI) (15). This compound can induce occupational asthma (37) in about 10% of workers involved in the production of plastics, adhesives, foams, surface coatings, and polyurethane polymers (20).…”

Inflammation-Induced Plasticity of the Afferent Innervation of the Airways

“…Exposure to TDI is associated with nasal irritation, rhinitis, and occupational asthma, and there is some evidence from animal models that activation of afferent C fibers plays a role in these responses (55). Acute exposure to inhaled TDI is associated with increased levels of mRNA encoding tachykinin precursor peptides in cell bodies of afferent fibers that innervate nasal mucosa as well as an increased density of substance P immunoreactive nerve fibers in rat nasal epithelium (54). These data suggest that exposure of airway epithelium to inhaled irritants can lead to increases in neuropeptide gene transcription and translation within the neuronal cell bodies located in sensory ganglia.…”

Sensory Neural Responses to Ozone Exposure during Early Postnatal Development in Rat Airways

“…SP released from sensory nerve fibers in the airway wall may contribute to the development of asthma through neurogenic inflammation, resulting in increased vascular permeability, chemotaxis of inflammatory cells, and smooth muscle hyperresponsiveness (15). In adult animal models, SP innervation of the airway wall is transiently increased after a wide range of airway irritants and exposures, including antigen challenge (10), Toluene diisocyanate exposure (16), viral infection (17), ozone (O 3 ) exposure (18), hypoxia (19), cigarette smoke (20), sulfur dioxide (12), and asphalt fume exposure (21). These studies imply that irritant-or allergen-induced increases of SP in airway sensory nerves may contribute to altered airway function.…”