Abstract
BackgroundAcute lung injury (ALI) is one of the most severe complications after orthotopic liver transplantation. Amplified inflammatory response after transplantation contributes to the process of ALI, but the mechanism underlying inflammation activation is not completely understood. We have demonstrated that mast cell stabilization attenuated inflammation and ALI in a rodent intestine ischemia/reperfusion model. We hypothesized that upregulation of inflammation triggered by mast cell activation may be involve in ALI after liver transplantation.MethodsAdult male Sprague–Dawley rats received orthotopic autologous liver transplantation (OALT) and were executed 4, 8, 16, and 24 h after OALT. The rats were pretreated with the mast cell stabilizers cromolyn sodium or ketotifen 15 min before OALT and executed 8 h after OALT. Lung tissues and arterial blood were collected to evaluate lung injury. β-hexosaminidase and mast cell tryptase levels were assessed to determine the activation of mast cells. Tumor necrosis factor α (TNF-α), interleukin (IL)-1β and IL-6 in serum and lung tissue were analyzed by enzyme-linked immunosorbent assay. Nuclear factor-kappa B (NF-κB) p65 translocation was assessed by Western blot.ResultsThe rats that underwent OALT exhibited severe pulmonary damage with a high wet-to-dry ratio, low partial pressure of oxygen, and low precursor surfactant protein C levels, which corresponded to the significant elevation of pro-inflammatory cytokines, β-hexosaminidase, and tryptase levels in serum and lung tissues. The severity of ALI progressed and maximized 8 h after OALT. Mast cell stabilization significantly inhibited the activation of mast cells, downregulated pro-inflammatory cytokine levels and translocation of NF-κB, and attenuated OALT-induced ALI.ConclusionsMast cell activation amplified inflammation and played an important role in the process of post-OALT related ALI.
Highlights
Liver transplantation is the most effective and efficient therapy for patients suffering from end-stage liver disease
We have previously reported that 58.2% of patients (91 patients in total) suffered from pulmonary complications after orthotopic liver transplantation (OLT), and about 27.5% of them suffered from Acute lung injury (ALI), and 5.5% of them endured adult respiratory distress syndrome (ARDS) [3]
We used 24 rats to investigate the effect of Mast cells (MCs) stabilization: eight rats were pretreated with cromolyn sodium, eight rats were pretreated with ketotifen, and eight rats were pretreated with the same volume of saline only
Summary
Liver transplantation is the most effective and efficient therapy for patients suffering from end-stage liver disease. Acute lung injury (ALI) is one of the most severe post-operative complications that potentially contribute to mortality after liver transplantation [2]. Given that complicated risk factors are associated with ALI after OLT, effective and preventive strategies are inadequate [4,5]. We have recently shown that rats suffering from ALI exhibited significant inflammatory response after OLT [11]. Acute lung injury (ALI) is one of the most severe complications after orthotopic liver transplantation. Amplified inflammatory response after transplantation contributes to the process of ALI, but the mechanism underlying inflammation activation is not completely understood. We have demonstrated that mast cell stabilization attenuated inflammation and ALI in a rodent intestine ischemia/reperfusion model. We hypothesized that upregulation of inflammation triggered by mast cell activation may be involve in ALI after liver transplantation
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
