Increased activation of the transcription factor c-Jun by MAP kinases in monocytes of multiple trauma patients is associated with adverse outcome and mass transfusion.
BACKGROUND
Post-traumatic dysfunction of the immune system is a major source of morbidity and mortality in patients with multiple trauma. The underlying intracellular mechanisms are still incompletely understood. Previous mRNA expression studies in monocytes suggested an involvement of the MAP kinases p38 and JNK and of the transcription factor c-Jun. Therefore, it was the aim of this study to elucidate whether alterations in the protein expression p38 MAPK, JNK, and c-Jun could be linked to PRBC substitution and survival.


METHODS
Thirty-seven patients with blunt multiple injuries and an ISS > 16 points were enrolled in our study. Blood was drawn on admission and 6, 12, 24, 48, and 72 h after the traumatic event. Monocytes were isolated immediately after sample collection and nuclear protein was extracted and phosphoprotein concentrations were measured. The resulting data were statistically analyzed.


RESULTS
An increased activation of MAP kinases and c-Jun could be shown in patients who died from their injuries. Additionally, patients who received PRBC substitution ≥10 units exhibited increased expression of activated MAP kinases and c-Jun.


CONCLUSIONS
We present a serial, sequential investigation in human monocytes of major trauma patients evaluating the activation of p38 MAPK, JNK and c-Jun in the post-traumatic period. We show that death after trauma and massive PRBC substitution are associated with activation of this pathway. The p38 MAPK, JNK, and c-Jun have well established proinflammatory properties. Therefore, it appears likely that this pathway is involved in the systemic hyperinflammatory states seen after massive PRBC transfusion and multiple trauma.
Department of Traumatology and Orthopedic Surgery, Ludwig-Maximilians University Munich, Munich, Germany. viktoria.bogner@med.uni-muenchen.de
Viktoria
V
Bogner
Veit
V
Stoecklein
Peter
P
Richter
Christian
C
Suren
Daniel
D
Teupser
Karl-Georg
KG
Kanz
Peter
P
Biberthaler
Wolf
W
Mutschler
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001803:Blood Transfusion; D005260:Female; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000201:enzymology / Q000276:immunology; D009104:Multiple Trauma / Q000276:immunology* / Q000378:metabolism* / Q000628:therapy; D010750:Phosphoproteins / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D016896:Treatment Outcome; D055815:Young Adult; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D010750:Phosphoproteins; D016755:Proto-Oncogene Proteins c-jun; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases