Acute lung injury induced by whole gastric fluid: hepatic acute phase response contributes to increase lung antiprotease protection

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dc.contributor.authorAyala, Pedro
dc.contributor.authorMeneses, Manuel
dc.contributor.authorOlmos Coelho, Pablo Roberto
dc.contributor.authorMontalva, Rebeca
dc.contributor.authorDroguett Quezada, Karla Denise.
dc.contributor.authorRios Raggio, Mariana
dc.contributor.authorBorzone, Gisella
dc.date.accessioned2019-10-17T13:45:31Z
dc.date.available2019-10-17T13:45:31Z
dc.date.issued2016
dc.date.updated2019-10-14T18:47:56Z
dc.description.abstractAbstract Background Gastric contents aspiration in humans is a risk factor for severe respiratory failure with elevated mortality. Although aspiration-induced local lung inflammation has been studied in animal models, little is known about extrapulmonary effects of aspiration. We investigated whether a single orotracheal instillation of whole gastric fluid elicits a liver acute phase response and if this response contributes to enrich the alveolar spaces with proteins having antiprotease activity. Methods In anesthetized Sprague-Dawley rats receiving whole gastric fluid, we studied at different times after instillation (4 h āˆ’7 days): changes in blood cytokines and acute phase proteins (fibrinogen and the antiproteases alpha1-antitrypsin and alpha2-macroglobulin) as well as liver mRNA expression of the two antiproteases. The impact of the systemic changes on lung antiprotease defense was evaluated by measuring levels and bioactivity of antiproteases in broncho-alveolar lavage fluid (BALF). Markers of alveolar-capillary barrier derangement were also studied. Non-parametric ANOVA (Kruskall-Wallis) and linear regression analysis were used. Results Severe peribronchiolar injury involving edema, intra-alveolar proteinaceous debris, hemorrhage and PMNn cell infiltration was seen in the first 24 h and later resolved. Despite a large increase in several lung cytokines, only IL-6 was found elevated in blood, preceding increased liver expression and blood concentration of both antiproteases. These changes, with an acute phase response profile, were significantly larger for alpha2-macroglobulin (40-fold increment in expression with 12-fold elevation in blood protein concentration) than for alpha1-antitrypsin (2ā€“3 fold increment in expression with 0.5-fold elevation in blood protein concentration). Both the increment in capillary-alveolar antiprotease concentration gradient due to increased antiprotease liver synthesis and a timely-associated derangement of the alveolar-capillary barrier induced by aspiration, contributed a 58-fold and a 190-fold increase in BALF alpha1-antitrypsin and alpha2-macroglobulin levels respectively (pā€‰<ā€‰0.001). Conclusions Gastric contents-induced acute lung injury elicits a liver acute phase response characterized by increased mRNA expression of antiproteases and elevation of blood antiprotease concentrations. Hepatic changes act in concert with derangement of the alveolar capillary barrier to enrich alveolar spaces with antiproteases. These findings may have significant implications decreasing protease burden, limiting injury in this and other models of acute lung injury and likely, in recurrent aspiration.
dc.fuente.origenBiomed Central
dc.identifier.citationRespiratory Research. 2016 Jun 14;17(1):71
dc.identifier.doi10.1186/s12931-016-0379-7
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/26648
dc.identifier.urihttps://doi.org/10.1186/s12931-016-0379-7
dc.issue.numeroNo. 71
dc.language.isoen
dc.pagina.final15
dc.pagina.inicio1
dc.revistaRespiratory Researches_ES
dc.rightsacceso abierto
dc.rights.holderThe Author(s).
dc.subject.ddc610
dc.subject.deweyMedicina y saludes_ES
dc.subject.otherJugo gƔstricoes_ES
dc.subject.otherPulmones - insuficienciaes_ES
dc.subject.otherPulmones - Enfermedadeses_ES
dc.titleAcute lung injury induced by whole gastric fluid: hepatic acute phase response contributes to increase lung antiprotease protectiones_ES
dc.typeartĆ­culo
dc.volumenVol. 17
sipa.codpersvinculados1013060
sipa.codpersvinculados98949
sipa.codpersvinculados50388
sipa.codpersvinculados99892
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