Recent evidence suggests that neurokinin (NK)-receptor activation may have a protective role in maintaining lung integrity when challenged by airborne toxicants such as sulfur dioxide, ozone, acrolein, or hydrocarbons. To investigate the effect of NK₁-receptor activation on hydrocarbon-induced lung injury, B6.A.D. (Ahr ^d/Nat^s) mice received subchronic exposures to JP-8 jet fuel (JP-8). Lung injury was assessed by the analysis of pulmonary physiology, bronchoalveolar lavage fluid, and morphology. Hydrocarbon exposure to target JP-8 concentrations of 50 mg/m³, with saline treatment, was characterized by enhanced respiratory permeability to ^99mTc-labeled diethylenetriaminepentaacetic acid, alveolar macrophage toxicity, and bronchiolar epithelial damage. Mice administered [Sar⁹,Met(O₂)¹¹]substance P, an NK₁-receptor agonist, after each JP-8 exposure had the appearance of normal pulmonary values and tissue morphology. In contrast, endogenous NK₁-receptor antagonism by CP-96345 administration exacerbated JP-8-enhanced permeability, alveolar macrophage toxicity, and bronchiolar epithelial injury. These data indicate that NK₁-receptor activation may have a protective role in preventing the development of hydrocarbon-induced lung injury, possibly through the modulation of bronchiolar epithelial function.

tachykinin; JP-8 jet fuel; inhalation; pulmonary toxicology

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