Avaliação dos mecanismos indutores da inflamação pulmonar decorrente da isquemia e reperfusão intestinal em camundongos geneticamente selecionados. / Evaluation of the mechanisms underlying the lung inflammation following intestinal ischemia / reperfusion (I/R) in genetically selected mice.
AUTOR(ES)
Tatiana Victoni
DATA DE PUBLICAÇÃO
2008
RESUMO
The aim of this study was to characterize the acute lung inflammation due to intestinal I/R in mice selected for high (AIRmax) or low (AIRmin) acute inflammatory response by means of bidirectional genetic selection. Balb/c mice were also used as a reference control of the parameters evaluated. Intestinal ischemia was induced by a 45-min clamping of the superior mesenteric artery; the clamping was then released and the lung inflammation was evaluated after a 4-h reperfusion period by measurements of myeloperoxidase (MPO) lung activity, leukocyte number (in blood, bone marrow and spleen), vascular permeability, cytokines (IL-1b, IL-10, IL-6 and TNF-a) and production of nitrates and nitrites in lung tissue ex vivo cultures (explants). Intestinal I/R induced an increase of the lung acute inflammatory reaction as judged by the increase of MPO activity and of vascular permeability and the influx of neutrophils in every animallineage studied, being the AIRmax mice the most reactive ones. However, the cellularity of the bone marrow and spleen was not affected by intestinal I/R in AIRmax or AIRmin mice. Intestinal I/R caused an increase of MPO activity in the gut of Balb/c, AIRmax and AIRmin mice, with no differences from each other. On the other hand, no intestinal plasma extravasation was noticed. Nitrites and nitrates production was higher in cultures of AIRmax mice lung explants after intestinal I/R. The spontaneous production of cytokines was not different among AIRmax and AIRmin lung explants, being significantly increased in AIRmax samples upon bacteriallipopolysaccharide (LPS) stimulation(IL-1b e IL-10). The profile of mortality among AIRmax and AIRmin was not altered by intestinal I/R. However, the mortality rate of injured AIRmin mice was found as early as 4 h after intestinal I/R, in contrast with that found in AIRmax animals (12 h after). In conclusion, our data suggest that genetically selected AIRmax and AIRmin mice react differentially to intestinal I/R, so that AIRmin mice show enhanced sensitivity (in terms of mortality rate), and their AIRmax counterparts show enhanced responsiveness (in terms of inflammatory response to I/R). Overall, we suggest that the genotypic changes due to selection may explain why an exacerbated inflammatory response to I/R in AIRmax mice coexists with a more favorable profile oflethality, whereas the opposite is seen in AIRmin animals.
ASSUNTO(S)
isquemia intestinal lung inflammation intestinal ischemia cytokines neutrophil inflamação pulmonar neutrófilo citocinas
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