Estudo do papel do receptor de quimiocina CCR2 no modelo experimental de lesão pulmonar associada à pancreatite aguda induzida pela administração de etanol e ácido palmitoleico

Abstract

Acute pancreatitis is an acute inflammatory disease of the exocrine pancreas that can involves remote organs including lung. Represent an important public health problem, with considerable morbidity and mortality, without specific treatment and pathogenesis remains obscure. Severe acute pancreatitis can lead to systemic inflammation and ARDS, responsible about 20% of mortality. Considering macrophages are important inflammatory cells in development of lung injury associated acute pancreatitis, and none of the experimental models are completely satisfactory until now, the aims of this work were to establish an acute pancreatitis model more adequately for the investigation of remote lung injury and to study the role of CCR2 in this pathogenesis. Our experimental model was induced by POA (200 mg/kg) and ethanol (1,8 g/kg) administration in C57Bl/6 mice. 24 hours later administration, we can observe amylase and lipase increase, cell recruitment in pancreas and worse of histopathological score in organ. In contrast, CCR2-/- animals were protected from lethality that can be related with decrease of macrophage infiltrate, normal levels of amylase and lipase, beyond of normal histopathological score in pancreas. Our results further showed high levels of CCL2 in serum of mice and increase of CXCL1 levels in WT compared with control and CCR2-/- mice. In lung, absence of CCR2 could reduce the neutrophil and macrophage influx to airway and protein exudation. However, we observed increased number of lymphocytes in BAL compared with WT mice. In lung tissue, we found there was a neutrophil accumulation in WT and CCR2-/- mice, but macrophage accumulation only in CCR2-/- mice. The pulmonary function assessment showed that our experimental model induced loss of lung function and absence of CCR2 avoids worsening of all parameters. Thus, our data suggest that our experimental model became interesting to study acute pancreatitis and associated lung injury, and CCR2 participate of local and systemic inflammatory process regulation.