Symptom control in severe asthmatics was not associated with airway tissue inflammation and remodeling, although persistent airflow obstruction in these patients was associated with bronchial inflammation and airway structural changes.

The environmental chemical 1,2-naphthoquinone (1,2-NQ) is implicated in the exacerbation of airways diseases induced by exposure to diesel exhaust particles (DEP), which involves a neurogenic-mediated mechanism. Plasma extravasation in trachea, main bronchus and lung was measured as the local (125)I-bovine albumin accumulation. RT-PCR quantification of TRPV1 and tachykinin (NK(1) and NK(2)) receptor gene expression were investigated in main bronchus. Intratracheal injection of DEP (1 and 5 mg/kg) or 1,2-NQ (35 and 100 nmol/kg) caused oedema in trachea and bronchus. 1,2-NQ markedly increased the DEP-induced responses in the rat airways in an additive rather than synergistic manner. This effect that was significantly reduced by L-732,138, an NK(1) receptor antagonist, and in a lesser extent by SR48968, an NK(2) antagonist. Neonatal capsaicin treatment also markedly reduced DEP and 1,2-NQ-induced oedema. Exposure to pollutants increased the TRPV1, NK(1) and NK(2) receptors gene expression in bronchus, an effect was partially suppressed by capsaicin treatment. In conclusion, our results are consistent with the hypothesis that DEP-induced airways oedema is highly influenced by increased ambient levels of 1,2-NQ and takes place by neurogenic mechanisms involving up-regulation of TRPV1 and tachykinin receptors.

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Agradecimentos Prof a. Dr a. Soraia Kátia Pereira Costa, por ter me recebido para realização do meu doutorado, orientação, serviço e dedicação a minha formação científica. Prof. Dr. Marcelo Nicolás Muscará, pela abertura do seu laboratório. Dr a. Sandra Sampaio, pela indispensável ajuda nos experimentos de fagocitose. Dr a. Carla Lima, pela ajuda nas dosagens de citocinas e discussões, e Dr a. Mônica Lopes Ferreira, pela abertura das portas do seu laboratório no Instituto Butantã. Dr a. Simone Aparecida Teixeira e Ana A. Varriano, pela indispensável ajuda na realização das técnicas in vitro. Dr a. Maria Teresa Ribela, pela marcação da albumina bovina com 125 I.

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