Activation of lung macrophage subpopulations in experimental acute pancreatitis

Pulmonary macrophages exist in two different anatomical compartments in the lower respiratory tract: alveolar macrophages in the alveoli and interstitial macrophages in the interstitium. Depending on the micro-environmental stimulation, macrophages follow different activation pathways. According to their inflammatory response pattern, activated macrophages have been characterized as pro-inflammatory (M1), wound-healing (M2a) and regulatory (M2b). Since acute pancreatitis occurs in parallel with acute lung injury, the profile of the different macrophage subpopulations could be relevant in the progression of the disease. The activation of lung alveolar and interstitial macrophages was assessed in an experimental model of severe acute pancreatitis induced in rats by intraductal infusion of 3.5% sodium taurocholate. Alveolar and interstitial macrophages were obtained and the expression of markers of different activations was evaluated. Activation of nuclear factors PPAR gamma and NF-kappa B, which are involved in the acquisition of different phenoytpes, was also measured. Alveolar macrophages acquired an early M1 phenotype characterized by the expression of inflammatory cytokines and NF-kappa B activation. In contrast, interstitial macrophages followed the inhibitory M2b pathway. In these macrophages, PPAR gamma became activated and the anti-inflammatory cytokine IL-10 was expressed. These results suggest that alveolar and interstitial macrophages play different roles in acute lung injury associated with acute pancreatitis. Alveolar macrophages promote an early inflammatory response, whereas interstitial macrophages help resolve inflammation. Copyright (C) 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.