Please use this identifier to cite or link to this item:
Title: Vesicular acetylcholine transport deficiency potentiates some inflammatory responses induced by diesel exhaust particles
Authors: SANTANA, Fernanda P. R.PINHEIRO, Nathalia M.BITTENCOURT-MERNAK, Marcia I.PERINI, AdenirYOSHIZAKI, KellyMACCHIONE, MariangelaSALDIVA, Paulo H. N.MARTINS, Milton A.TIBERIO, Iolanda F. L. C.PRADO, Marco Antonio M.PRADO, Vania F.PRADO, Carla M.
Citation: ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY, v.167, p.494-504, 2019
Abstract: Endogenous acetylcholine (ACh), which depends of the levels of vesicular ACh transport (VAChT) to be released, is the central mediator of the cholinergic anti-inflammatory system. ACh controls the release of cytokine in different models of inflammation. Diesel exhaust particles (DEP) are one of the major environmental pollutants produced in large quantity by automotive engines in urban center. DEP bind the lung parenchyma and induce inflammation. We evaluated whether cholinergic dysfunction worsens DEP-induced lung inflammation. Male mice with decreased ACh release due to reduced expression of VAChT (VAChT-KD mice) were submitted to DEP exposure for 30 days (3 mg/mL of DEP, once a day, five days a week) or saline. Pulmonary function and inflammation as well as extracellular matrix fiber deposition were evaluated. Additionally, airway and nasal epithelial mucus production were quantified. We found that DEP instillation worsened lung function and increased lung inflammation. Higher levels of mononuclear cells were observed in the peripheral blood of both wild-type (WT) and VAChT-KD mice. Also, both wild-type (WT) and VAChT-KD mice showed an increase in macrophages in bronchoalveolar lavage fluid (BALF) as well as increased expression of IL-4, IL-6, IL-13, TNF-alpha, and NF-kappa B in lung cells. The collagen fiber content in alveolar septa was also increased in both genotypes. On the other hand, we observed that granulocytes were increased only in VAChT-KD peripheral blood. Likewise, increased BALF lymphocytes and neutrophils as well as increased elastic fibers in alveolar septa, airway neutral mucus, and nasal epithelia acid mucus were observed only in VAChT-KD mice. The cytokines IL-4 and TNF-alpha were also higher in VAChT-KD mice compared with WT mice. In conclusion, decreased ability to release ACh exacerbates some of the lung alterations induced by DEP in mice, suggesting that VAChT-KD animals are more vulnerable to the effects of DEP in the lung.
Appears in Collections:

Artigos e Materiais de Revistas Científicas - FM/MCM
Departamento de Clínica Médica - FM/MCM

Artigos e Materiais de Revistas Científicas - FM/MPT
Departamento de Patologia - FM/MPT

Artigos e Materiais de Revistas Científicas - HC/ICHC
Instituto Central - HC/ICHC

Artigos e Materiais de Revistas Científicas - HC/InCor
Instituto do Coração - HC/InCor

Artigos e Materiais de Revistas Científicas - LIM/05
LIM/05 - Laboratório de Poluição Atmosférica Experimental

Artigos e Materiais de Revistas Científicas - LIM/20
LIM/20 - Laboratório de Terapêutica Experimental

Files in This Item:
File Description SizeFormat 
  Restricted Access
publishedVersion (English)2.71 MBAdobe PDFView/Open Request a copy

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.