Toluene diisocyanate inhalation enhances substance P immunoreactivity and preprotachykinin mRNA expression in trigeminal neurons innervating the nasal epithelium.
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1998/04/30
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Description:Inhalation of irritants, like toluene diisocyanate (TOI), stimulates the release of substance P (SP) from peripheral processes of sensory neurons that innervate the airways. The purpose of this study was to determine if TOI inhalation affects intraneuronal levels of SP and preprotachykinin (PPT) mRNA in the sensory neurons of the trigeminal ganglion (TG) which innervate the respiratory epithelium of the nasal cavity. The nasal cavity of Fisher-344 male rats was instilled with rhodamine-labeled latex microspheres to identify neurons in the TG projecting to the nasal epithelium. Ten days after tracer application, the rats were exposed to 60 ppb of 2,4-2,6-TDI vapor for two hours. The TG were removed 1, 12, 24, 48, 72 and 96 hours after TOI-treatment and prepared for SP-immunocytochemistry and PPT in situ hybridization. SP nerve fiber density was measured in nasal mucosal tissues using immunocytochemistry. SP nerve fiber density (% nerve fiber area) was significantly increased 12, 24 and 48 hrs after TOI exposure. The proportion of microsphere-labeled cell bodies expressing high levels of SP immunoreactivity was decreased at 24 hrs but was increased above controls at 48 and 72 hrs. The proportion of microspherelabeled cell bodies expressing high levels of PPT mRNA was increased above control levels at 24 and ·48 hrs. All changes in SP immunoreactivity and PPT mRNA levels had recovered to control levels 96 hours after TOI inhalation. The percentage of leukocytes observed in nasal lavage fluid was significantly increased 1, 12, 24, 48 and 72 after inhalation and returned to control levels 96 hr after inhalation. These studies indicate that SP production in TG neurons projecting to the nasal epithelium is transiently increased after a single TOI exposure suggesting that TOI inhalation not only causes SP release but also increased intraneuronal neuropeptide levels. Increased neuronal SP levels may be involved in maintaining neurogenic inflammation or contribute to the development of airway hypreresponsiveness.
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Pages in Document:1-26
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NIOSHTIC Number:nn:20057251
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Citation:Occupational asthma: in and out of the workplace conference, April 30 - May 2, 1998, Morgantown, West Virginia. Morgantown, WV: U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, 1998 Apr; :1-26
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Federal Fiscal Year:1998
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Peer Reviewed:False
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Source Full Name:Occupational asthma: in and out of the workplace conference, April 30 - May 2, 1998, Morgantown, West Virginia
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Main Document Checksum:urn:sha-512:015cbc3146e454a3062fd696612fe892d0235a96aca7f2a427a5d463520b6887df71f13f1b88606ad1968ea37a47b7b45a376ec089c9156071a662aa8c956a48
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