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Lung Edema and Mortality Induced by Intestinal Ischemia and Reperfusion Is Regulated by VAChT Levels in Female Mice

Inflammation, 2021-08, Vol.44 (4), p.1553-1564 [Peer Reviewed Journal]

The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2021 ;2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. ;The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2021. ;ISSN: 0360-3997 ;EISSN: 1573-2576 ;DOI: 10.1007/s10753-021-01440-z ;PMID: 33715111

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Title:
Lung Edema and Mortality Induced by Intestinal Ischemia and Reperfusion Is Regulated by VAChT Levels in Female Mice
Author: Santana, Fernanda P. R. ; Ricardo-da-Silva, Fernanda Y. ; Fantozzi, Evelyn T. ; Pinheiro, Nathália M. ; Tibério, Iolanda F. L. C. ; Moreira, Luiz Felipe Pinho ; Prado, Marco Antônio M. ; Prado, Vânia F. ; Tavares-de-Lima, Wothan ; Prado, Carla Máximo ; Breithaupt-Faloppa, Ana Cristina
Subjects: Acetylcholine receptors (nicotinic) ; Animals ; Biomedical and Life Sciences ; Biomedicine ; Cytokines ; Edema ; Female ; Genotypes ; Immunology ; Inflammation ; Inflammation Mediators - metabolism ; Internal Medicine ; Intestine ; Intestines - blood supply ; Intestines - metabolism ; Ischemia ; Lungs ; Mice ; Mice, Transgenic ; Mortality ; Oophorectomy ; Original Article ; Ovariectomy ; Ovariectomy - adverse effects ; Ovariectomy - mortality ; Pathology ; Permeability ; Peroxidase ; Pharmacology/Toxicology ; Protein transport ; Pulmonary Edema - metabolism ; Pulmonary Edema - mortality ; Reperfusion ; Reperfusion Injury - metabolism ; Reperfusion Injury - mortality ; Rheumatology ; Sex hormones ; Vesicular Acetylcholine Transport Proteins - metabolism
Is Part Of: Inflammation, 2021-08, Vol.44 (4), p.1553-1564
Description: Acute lung injury induced by intestinal ischemia/reperfusion (I/R) is a relevant clinical condition. Acetylcholine (ACh) and the α7 nicotinic ACh receptor (nAChRα-7) are involved in the control of inflammation. Mice with reduced levels of the vesicular ACh transporter (VAChT), a protein responsible for controlling ACh release, were used to test the involvement of cholinergic signaling in lung inflammation due to intestinal I/R. Female mice with reduced levels of VAChT (VAChT-KD HOM ) or wild-type littermate controls (WT) were submitted to intestinal I/R followed by 2 h of reperfusion. Mortality, vascular permeability, and recruitment of inflammatory cells into the lung were investigated. Parts of mice were submitted to ovariectomy (OVx) to study the effect of sex hormones or treated with PNU-282,987 (nAChRα-7 agonist). A total of 43.4% of VAChT-KD HOM -I/R mice died in the reperfusion period compared to 5.2% of WT I/R mice. The I/R increased lung inflammation in both genotypes. In VAChT-KD HOM mice, I/R increased vascular permeability and decreased the release of cytokines in the lung compared to WT I/R mice. Ovariectomy reduced lung inflammation and permeability compared to non-OVx, but it did not avoid mortality in VAChT-KD HOM -I/R mice. PNU treatment reduced lung permeability, increased the release of proinflammatory cytokines and the myeloperoxidase activity in the lungs, and prevented the increased mortality observed in VAChT-KD HOM mice. Cholinergic signaling is an important component of the lung protector response against intestinal I/R injury. Decreased cholinergic signaling seems to increase pulmonary edema and dysfunctional cytokine release that increased mortality, which can be prevented by increasing activation of nAChRα-7. Graphical abstract
Publisher: New York: Springer US
Language: English
Identifier: ISSN: 0360-3997
EISSN: 1573-2576
DOI: 10.1007/s10753-021-01440-z
PMID: 33715111
Source: MEDLINE
ProQuest Central

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Lung Edema and Mortality Induced by Intestinal Ischemia and Reperfusion Is Regulated by VAChT Levels in Female Mice

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