Vesicular acetylcholine transport deficiency potentiates some inflammatory responses induced by diesel exhaust particles

Autor(es):Mostrar menos -

Santana, Fernanda P. R. ^{[1, 2]} ; Pinheiro, Nathalia M. ^[2] ; Bittencourt-Mernak, Marcia I. ^[1] ; Perini, Adenir ^[2] ; Yoshizaki, Kelly ^[3] ; Macchione, Mariangela ^[3] ; Saldiva, Paulo H. N. ^[3] ; Martins, Milton A. ^[2] ; Tiberio, Iolanda F. L. C. ^[2] ; Prado, Marco Antonio M. ^{[4, 5]} ; Prado, Vania F. ^{[4, 5]} ; Prado, Carla M. ^{[2, 6]}

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, Dept Biol Sci, Diadema - Brazil

^[2] Univ Sao Paulo, Sch Med, Dept Med, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Sch Med, Dept Pathol, Sao Paulo - Brazil

^[4] Univ Western Ontario, Dept Physiol & Pharmacol, London, ON - Canada

^[5] Univ Western Ontario, Dept Anat & Cell Biol, London, ON - Canada

^[6] Univ Fed Sao Paulo, Dept Biosci, Rua Silva Jardim, 136 Vila Mathias, BR-11015020 Santos, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY; v. 167, p. 494-504, JAN 15 2019.
• Citações Web of Science: 2

Resumo

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. (AU)

• Processo FAPESP: 08/55359-5 - Avaliação da função e da histopatologia pulmonar em modelo experimental de redução da função colinérgica em camundongos geneticamente modificados
• Beneficiário: Carla Máximo Prado
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 14/25689-4 - Efeito do sistema colinérgico na inflamação pulmonar aguda e crônica.
• Beneficiário: Carla Máximo Prado
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 11/15817-7 - Efeito da hipofunção colinérgica na mecânica e na histopatologia pulmonar em modelo experimental de inflamação pulmonar induzida por instilação de poluente em camundongos
• Beneficiário: Fernanda Paula Roncon Santana Novelli
• Modalidade de apoio: Bolsas no Brasil - Mestrado