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.
Sakiyama
Shoji
S
Thoracic Surgery Research Laboratory, University Health Network Toronto General Hospital and Department of Surgery and Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
Hamilton
Julia
J
Han
Bing
B
Jiao
Yang
Y
Shen-Tu
Grace
G
de Perrot
Marc
M
Keshavjee
Shaf
S
Liu
Mingyao
M
D000293:Adolescent; D000328:Adult; D015153:Blotting, Western; D016923:Cell Death; D015180:Electrophoresis, Gel, Two-Dimensional; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005260:Female; D006801:Humans; D015151:Immunoblotting; D007249:Inflammation; D016040:Lung Transplantation / Q000009:adverse effects*; D048670:MAP Kinase Kinase 4 / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D015427:Reperfusion Injury / Q000201:enzymology* / Q000503:physiopathology; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4