The involvement of sensory neuropeptides in toluene diisocyanate‐induced tracheal hyperreactivity in the mouse airways

Abstract

1 Recently, we developed a murine model to investigate toluene diisocyanate (TDI)-induced occupational asthma. After skin-sensitization and intranasal challenge with TDI (1%) mice exhibited tracheal hyperreactivity 24 h after the challenge. 2 The aim of the present study was to investigate the possible role for sensory neuropeptides in the development of this tracheal hyperreactivity. 3 First, we demonstrated that direct application of TDI in vitro induced the release of tachykinins from the sensory nerves in the mouse isolated trachea. Second, capsaicin pretreatment, resulting in the depletion of sensory neuropeptides, completely abolished the TDI-induced tracheal hyperreactivity 24 h after the challenge. Third, the selective neurokinin, (NK1)-receptor antagonist RP 67580 (0.2 Mumol kg-') also inhibited tracheal hyperreactivity when it was administered before the challenge. However, administration of RP 67580 during the sensitization phase did not result in a suppression of the TDIinduced tracheal hyperreactivity 24 after the challenge. 4 When TDI-sensitized mice were topically challenged with TDI a marked ear swelling response was observed. The cutaneous response after TDI application was not affected by capsaicin pretreatment or RP 67580 administration. 5 These results clearly show that sensory neuropeptides, particularly tachykinins, are essential for the development of TDI-induced tracheal hyperreactivity during the effector phase. The differences between the airways and skin with respect to the sensory neuropeptides is intriguing and could suggest a local action for the tachykinins in the airways.

The role of tachykinin receptor antagonists in the prevention of bronchial hyperresponsiveness, airway inflammation and cough

“…However, the results obtained with selective tachykinin NK 2 receptor antagonists, such as SR 48968 and MEN 10,627, strongly suggest that tachykinins are involved in the development of airway hyperresponsiveness, and that tachykinin NK 2 receptor stimulation plays an important role in this phenomenon, in the guineapig. It was reported that tachykinins are essential for the development of tracheal hyperreactivity induced by toluene diisocyanate in mouse airways [62]. In contrast to the prevention of airway hyperresponsiveness by the tachykinin NK 2 receptor antagonist in guinea-pig, the hyperresponsiveness observed in the mouse was completely blocked by the tachykinin NK 1 receptor antagonist, RP 67,580 [62].…”

“…It was reported that tachykinins are essential for the development of tracheal hyperreactivity induced by toluene diisocyanate in mouse airways [62]. In contrast to the prevention of airway hyperresponsiveness by the tachykinin NK 2 receptor antagonist in guinea-pig, the hyperresponsiveness observed in the mouse was completely blocked by the tachykinin NK 1 receptor antagonist, RP 67,580 [62].…”

“…of capsaicin, which depletes tachykinins from NANC nerves, eliminated airway hyperresponsiveness induced by acute capsaicin [48], citric acid [53], ovalbumin [54,55] toluene diisocyanate [56], endotoxin [57], plateletactivating factor (PAF) [58], respiratory viral infection [59], and ozone [60] in guinea-pigs, dinitro-fluorobenzene [61] and toluene diisocyanate [62] in mice, and Altenaria tenuis aerosol in rabbits [63].…”

Toluene diisocyanate (TDI) induces calcium elevation and interleukine-4 (IL-4) release - Early responses upon TDI stimulation

“…The general public may be exposed to TDI through emissions from urethane foam production facilities. In the -rogenic factors might be involved (Mapp et al, 1994b;Scheerens et al, 1996). Vanoirbeek found in 2009 that an elevation in immunoglobulin-E (IgE) under TDI treatments (Vanoirbeek et al, 2009) which can explain the TDI-induced allergy although TDI can induce allergies through IgE independent pathways mentioned in some literature.…”

Neurogenic Inflammation and Particulate Matter (PM) Air Pollutants

“…The in¯ammation and airway hyper-responsiveness associated with a variety of air pollutants are reduced in animals whose sensory ®bers have been destroyed by capsaicin-treatments or interrupted with antagonists to neuropeptide or capsaicin receptors (Prior et al, 1990;Nielsen, 1991;Yeadon et al, 1992;Satoh et al, 1993;Scheerens et al, 1996). The relevance of sensory innervation and its irritant receptors to ROFA in¯ammation was subsequently examined in a murine model of airway hyper-responsiveness.…”