Pancreatitis-Associated Pulmonary Injury
Abstract: In acute pancreatitis (AP), lung injury is an early occuring and important part of the multiple organ dysfunction syndrome. The mechanisms underlying the development of lung injury though still largely remains unclear. The aim of the present study was to study mechanisms of the systemic and secondary pulmonary inflammation and injury, with an emphasis on the involvement of immune cells, inflammatory mediators. AP was induced by intraductal infusion of 5% sodium taurodeoxycholate in the rat. Abdominal sepsis (AS) was induced by cecal ligation and puncture. Pulmonary endothelial barrier dysfunction (EBD), protein content, protease activity, cytokines and chemokines were accessed. Adhesion molecule (PECAM-1, ICAM-1, L-selectin) expression on neutrophils and monocytes/macrophages (Mo/Mf) was measured by flowcytometry. Plasma exsudation to the lungs increased early on in AP and later in AS. Adhesion molecules on cells from the circulation, bronchoalveolar lavage fluid and lung tissue exhibited different expression patterns at different time-points. Leukocyte recruitment increased early on and persisted at all time-points. The mast cell stabilizer cromolyn prevented against a decrease in expression of PECAM-1 on circulatory neutrophils and Mo/Mf and against an increased expression of ICAM-1 and PECAM-1 on pulmonary neutrophils and Mo/Mf 6h in AP. EBD was prevented by cromolyn pretreatment. Pretreatment with polymyxin B prevented against acute pancreatitis-induced lung injury and the otherwise occurring increases in TNF-a, MCP-1 IL-1b, and IL-10, as well as against the decreases in IL-2, IFN-gamma and TIMP-1, decreased protease activity and down-regulation of CD31, CD54, and CD62-L on recruited neutrophils and Mo/Mf in BALF. Our results imply that different activation mechanisms exist through the course of pancreatitis-induced lung injury. Mast cell activation seems involved in the development of pancreatitis-induced lung injury, an injury that might be direct or through activation of other immune cells. Cells at different locations exhibit different expression and activation patterns at the same time points. Inhibition of PKC prevented against the development of pancreatitis-associated lung injury.
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