Connective tissue mast cells are the target of formaldehyde to induce tracheal hyperresponsiveness in rats: Putative role of leukotriene B-4 and nitric oxide

Autor(es)

Lino-dos-Santos-Franco, Adriana ; Shia, Mey Kuang ; Domingos, Helori Vanni ; Breithaupt-Faloppa, Ana Cristina ; Ligeiro de Oliveira, Ana Paula ; Oliveira-Filho, Ricardo Martins ; Vargaftig, B. Boris ; Tavares-de-Lima, Wothan ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Ciencias Biomed, Lab Fisiopatol Inflamacao Expt, Dept Pharmacol, BR-05508900 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Toxicology Letters; v. 192, n. 2, p. 85-90, FEB 1 2010.
• Citações Web of Science: 4

Resumo

Formaldehyde (FA) exposure induces upper airways irritation and respiratory abnormalities, but its mechanisms are not understood. Since mast cells are widely distributed in the airways, we hypothesized that FA might modify the airways reactivity by mechanism involving their activation. Tracheal rings of rats were incubated with Dulbecco's modified medium culture containing FA (0.1 ppm) in 96-well plastic microplates in a humid atmosphere. After 30 min, 6 h, and 24-72 h, the rings were suspended in an organ bath and dose-response curve to methacholine (MCh) were determined. incubation with FA caused a transient tracheal hyperresponsiveness to MCh that was independent from tracheal epithelium integrity. Connective tissue mast cell depletion caused by compound 48/80 or mast cell activation by the allergic reaction, before exposure of tracheal rings to FA prevented the increased responsiveness to MCh. LTB(4) concentrations were increased in the culture medium of tracheas incubated with FA for 48 h, whereas the LTB(4)-receptor antagonist MK886 (1 mu M) added before FA exposure rendered the tracheal rings normoreactive to MCh. In addition, FA exposure did not cause hyperresponsiveness in tracheal segments incubated with L-arginine (1 mu M). We suggest that airway connective tissue mast cells constitute the target and may provide the increased LTB(4) generation as well as an elevated consumption of NO leading to tracheal hyperresponsiveness to MCh. (C) 2009 Elsevier Ireland Ltd. All rights reserved. (AU)

• Processo FAPESP: 08/50766-1 - Repercussao pulmonar e sistemica apos exposicao de ratos ao formaldeido: papel regulador das especies reativas derivadas do oxigenio e do nitrogenio.
• Beneficiário: Adriana Lino dos Santos Franco
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 02/06606-3 - Fatores moduladores da inflamacao pulmonar experimental.
• Beneficiário: Wothan Tavares de Lima
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 01/11417-2 - Efeitos da exposicao ao formaldeido sobre a sensibilizacao e desencadeamento de inflamacao alergica pulmonar em ratos.
• Beneficiário: Adriana Lino dos Santos Franco
• Modalidade de apoio: Bolsas no Brasil - Mestrado