title: Inhalation of toluene diisocyanate is associated with increased production of nitric oxide by rat bronchoalveolar lavage cells.
abstract: Isocyanates are used commercially, particularly in the manufacture of polyurethane coatings and foam. These compounds can pose an occupational health hazard since there is a risk of respiratory disease following isocyanate exposure. The purpose of the present study was to investigate whether a single, sublethal isocyanate inhalation is associated with increased production of the free radical nitric oxide (NO). Mature male Sprague-Dawley rats were exposed to air or toluene diisocyanate (TDI; 2 ppm) for 4 hr. Indices of pulmonary function were assessed before and after exposure to TDI fumes. At 20 hr postexposure, bronchoalveolar lavage cells (BALC) and fluid were harvested. NO synthase (NOS)-dependent reactive species production by alveolar macrophages was assessed by determining N(omega)-nitro-L-arginine methyl ester-inhibitable chemiluminescence following stimulation with unopsonized zymosan. Northern blot analysis was used to index inducible NOS mRNA levels in BALC, while nitrite and nitrate (NOx) levels were measured to determine NOx levels in the lavage fluid and the production of NO by cultured adherent BALC was indexed by measuring nitrite levels. Exposure to aerosolized TDI was associated with an increase in the number of alveolar macrophages, lymphocytes, and polymorphonuclear leukocytes harvested by bronchoalveolar lavage, relative to that from air-exposed rats. NOx levels in the lavage fluid and NOS-dependent production of reactive species by alveolar macrophages were increased following TDI exposure. In addition, inducible NO production by BALC (i.e., mRNA levels and nitrite levels in BALC conditioned media) was elevated following TDI treatment. These findings indicate that pulmonary inflammatory responses induced by TDI exposure are associated with increases in inducible NO production. Therefore, the potential role of NO in the initial pulmonary response to TDI exposure warrants further investigation.
authors.affiliation: Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, West Virginia 26505-2888, USA.
authors.forename: L J
authors.initials: LJ
authors.lastname: Huffman
authors.forename: D J
authors.initials: DJ
authors.lastname: Judy
authors.forename: D
authors.initials: D
authors.lastname: Frazer
authors.forename: R E
authors.initials: RE
authors.lastname: Shapiro
authors.forename: V
authors.initials: V
authors.lastname: Castranova
authors.forename: M
authors.initials: M
authors.lastname: Billie
authors.forename: H V
authors.initials: HV
authors.lastname: Dedhia
mesh_terms: D000280:Administration, Inhalation; D000388:Air; D000818:Animals; D001120:Arginine / Q000633:toxicity; D015152:Blotting, Northern; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology*; D002478:Cells, Cultured; D004790:Enzyme Induction / Q000187:drug effects; D007249:Inflammation / Q000139:chemically induced; D008163:Luminescent Measurements; D016676:Macrophages, Alveolar / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000633:toxicity; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D012129:Respiratory Function Tests; D014051:Toluene 2,4-Diisocyanate / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D015054:Zymosan / Q000494:pharmacology
chemical_list: D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D014051:Toluene 2,4-Diisocyanate; D009569:Nitric Oxide; D015054:Zymosan; D001120:Arginine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester