Activation of alveolar macrophages in lung injury associated with experimental acute pancreatitis is mediated by the liver

Objective To evaluate (1) whether alveolar macrophages are activated as a c onsequence of acute pancreatitis (AP), (2) the implication of inflammatory factors released by these macrophages in the process of neutrophil migratio n into the lungs observed in lung injury induced by AP, and (3) the role of the liver in the activation of alveolar macrophages; Summary Background Data Acute lung injury is the extrapancreatic complicati on most frequently associated with death and complications in severe AP. Ne utrophil infiltration into the lungs seems to be related to the release of systemic and local mediators. The liver and alveolar macrophages are source s of mediators that have been suggested to participate in the lung damage a ssociated with AP. Methods Pancreatitis was induced in rats by intraductal administration of 5 % sodium taurocholate. The inflammatory process in the Lung damage lung and the activation of alveolar macrophages were investigated in animals with a nd without portocaval shunting 3 hours after AP induction, Alveolar macroph ages were obtained by bronchoalveolar ravage. The generation of nitric oxid e, leukotriene B-4, tumor necrosis factor-alpha, and MIP-2 by alveolar macr ophages and the chemotactic activity of supernatants of cultured macrophage s were evaluated. Results Pancreatitis was associated with increased infiltration of neutroph ils into the lungs 3 hours after induction. This effect was prevented by th e portocaval shunt. Alveolar macrophages obtained after induction of pancre atitis generated increased levels of nitric oxide, tumor necrosis factor-al pha, and MIP-2; but not leukotriene B-4. In addition, supernatants of these macrophages exhibited a chemotactic activity for neutrophils when instille d into the lungs of unmanipulated animals. All these effects were abolished when portocaval shunting was carried out before induction of pancreatitis. Conclusion Lung damage induced by experimental AP is associated with alveol ar macrophage activation. The liver mediates the alveolar macrophage activa tion in this experimental model.