Significant decline of peripheral myeloid dendritic cells following multiple trauma.

BACKGROUND: Dendritic cells (DC) represent an important and integral part of the immune system and are potent initiators of inflammation. Two distinct subsets of DC have been identified: myeloid DC (MDC) and plasmacytoid DC (PDC), which differ widely in many respects. Despite the importance of the DC in the inflammatory response that occurs after severe multiple injury, there is a profound lack of information regarding the distribution and regulation of DC subtypes following multiple trauma. The main goal of this study was to assess whether the normal distribution of circulating DC subpopulations is altered during the first 5 d after multiple trauma. PATIENTS AND METHODS: Sixty-three patients with multiple trauma (ISS 31 +/- 15 points) and 11 healthy volunteers (control group) were enrolled. Blood samples were taken on admission (D0) and daily for the following 5 d. The percentages of MDC and PDC were determined by flow cytometry. RESULTS: A significant decline of the MDC concentration was observable on days 3 to 5 after admission in comparison to the values obtained on the day of admission. The ratio of MDC to PDC decreased significantly (3-fold, P < 0.05). This reduction correlated significantly with changes observed in the plasma concentrations of IL-10 (r = 0.5; P < 0.05). DISCUSSION: Our data demonstrate that multiple trauma is followed by a marked change in the subpopulation composition of the DC compartment, and that these changes are inversely associated with enhanced IL-10 plasma concentrations. This imbalance in the DC compartment favoring PDC concentrations may contribute to the immunological alterations that are observed following multiple trauma.

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

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.