Molecular Profiling of Experimental Blunt Chest Trauma

Abstract

Trauma to the chest still causes approximately a quarter of all trauma-related deaths and pulmonary contusion itself has an age-dependent mortality up to 42%. Here we explore the diverse transcriptional programs activated after blunt thoracic trauma, which is still poorly understood. Bilateral lung injury was induced in rats by a single blast wave, followed by RNA-isolation and microarray analysis at various time points after trauma (0–24h post-trauma). To determine the protective effects of a systemic C5a-blockade in the 3h post trauma window, either pre-immune IgG or anti-C5a IgG was applied intravenously. During the early post-traumatic phase, proteins of the intracellular PIP3-kinase pathway were significantly downregulated, while various cytokines and their receptors were upregulated. Proteins encoding for the coagulation system were massively upregulated. Whereas the expression of the complement split product C4a was consistently reduced, C3 was upregulated 12h post injury. In the late post-traumatic phase, MAP-kinase and ion-channels were also affected and down-regulated. While various important complement players, MAP-kinase and the bradykinin-receptor were down-regulated 3h post injury in IgG-treated animals, systemic C5a blockade after trauma led to a more transcriptional balance program similar to the sham treated group. These data might lead to a better understanding of the molecular signature after severe trauma and reveal new therapeutic targets to prevent the severe consequences of blunt chest trauma. This work was supported by NIH Grants No. GM-61656, GM-29507 and HL-31963.