Activation of mitogen-activated protein kinases during human lung transplantation

Background: Ischemia-reperfusion is one of the unavoidable steps in lung transplantation; it is associated with acute inflammatory responses and cell death. The intracellular signal transduction mechanisms of these events are largely unknown. We hypothesize that activation of mitogen-activated protein kinases (MAPKs) is one of the important signaling events during human lung transplantation. Methods: Lung tissue biopsies were performed on 15 patients undergoing transplantation: after cold ischemic preservation; after warm, ischemia (implantation); and after 1- or 2-hour reperfusion. The phosphorylation status of MAPK isoforms (ERK, p38-MAPK and JNK) was examined by Western blotting. Results: Phosphorylation of ERK was dramatically increased during the first 2 hours of reperfusion. Phosphorylation of JNK also significantly increased at lower levels. In contrast, phosphorylation of p38 showed no significant changes. Conclusions: We speculate that the rapid and sustained activation of ERK and JNK during the early reperfusion period may contribute to acute inflammatory responses and cell death of lung grafts.