Altered gene expression patterns in dendritic cells after severe trauma: implications for systemic inflammation and...

Dendritic cells (DCs) are professional antigen-presenting cells and members of the adoptive immunity. In addition, they play an important role in innate immunity within the systemic inflammatory response to trauma and sepsis. In this study, gene expression patterns of DC in patients with multiple trauma were studied. Total RNA was isolated from highly purified DCs (purity>95%) that were enriched from peripheral blood mononuclear cells and whole blood, respectively. Samples were obtained from 10 multiple trauma patients (injury severity score, 35.4+/-10.6 on day of admission) and 5 healthy volunteers (control). Aliquots of target cDNAs and reference samples (cDNA derived from the monocytic cell line SIGM5) were cohybridized on a thematic medium-density microarray assessing 780 inflammation-related transcripts. Twenty transcripts were up-regulated in DCs of multiple trauma patients compared with healthy volunteers, whereas these differences were missed when RNA from whole blood was subjected to transcriptomic profiling. This cluster included central effector molecules of DC such as transcripts encoding for 5-lipoxygenase and the corresponding leukotriene 4 receptor, which regulate DC migration, adoptive immune responses, and airway inflammation, as well as CD74, CXCL4, or platelet factor 4, a chemokine not implicated as a product of DCs to date. In addition, genes involved in antiapoptosis (BCL2), intracellular signal transduction (mitogen-activated protein kinase), and secretion of mediators (VAMP2) were found to be up-regulated. The up-regulated transcripts suggest that life span and signaling function of DCs are altered by trauma. Furthermore, these data confirm and expand the central role of chemokines and lipid mediators as effector molecules of DC-mediated immune responses in systemic inflammation associated with severe trauma.