Aged Human Stored Red Blood Cell Supernatant Inhibits Macrophage Phagocytosis in an HMGB1 Dependent Manner After Trauma in a Murine Model:

Red blood cell transfusions in the setting of trauma is a double edged sword, as it is a necessary component for life-sustaining treatment in massive hemorrhagic shock, but also associated with increased risk for nosocomial infections and immune suppression. The mechanisms surrounding this immune suppression are unclear. Using supernatant from human packed red blood cell (RBC), we demonstrate that clearance of E. coli by macrophages is inhibited both in vitro and in vivo using a murine model of trauma and hemorrhagic shock. We further explore the mechanism of this inhibition by demonstrating that human stored RBCs contain soluble high mobility group box 1 protein (HMGB1) which increases throughout storage. HMGB1 derived from the supernatant of human stored RBCs was shown to inhibit bacterial clearance, as neutralizing antibodies to HMGB1 restored the ability of macrophages to clear bacteria. These findings demonstrate that extracellular HMGB1 within stored RBCs could be one factor leading to immune suppression following transfusion in the trauma setting

Influence of drying by convective air dryer and ultrasound on the vitamin C and β–carotene of carrots

Convective air drying and power ultrasound effects on vitamin C and β-carotene contents in carrots were studied. For convective air drying, a central composite face-centered design fitting temperature between 40 and 65 C and air flow rate between 2 and 6 10-1 m/s were used; previously, carrots were blanched. Likewise, ultrasound drying was performed on both unblanched and blanched carrots at 20, 40, and 60 C for 120, 90, and 75 min, respectively. Blanching had a sharp effect on vitamin C and β-carotene degradation (80-92% retentions, respectively), and convective air drying led to further losses (32-50% and 73-90% retentions, respectively). According to the response surface model, a combination of 40 C and 6 10-1 m/s will maximize vitamin C retention in dried carrots, whereas 40 C and 3.3 10-1 m/s will ensure the highest β-carotene content. Ultrasound drying caused higher vitamin C and β-carotene retention (82-92% and 96-98%, respectively) than convective air drying. Blanched carrots dehydrated by ultrasound showed retentions of 55% and 88% of vitamin C and β-carotene, respectively. Ultrasound drying at 20 C for 120 min caused the maximum vitamin C and β-carotene contents. Therefore, power ultrasound may be considered a valuable tool to obtain high nutritive dehydrated carrotsPeer reviewe

Toll-Like Receptor 4 on both Myeloid Cells and Dendritic Cells Is Required for Systemic Inflammation and Organ Damage after Hemorrhagic Shock with Tissue Trauma in Mice

Trauma combined with hemorrhagic shock (HS/T) leads to systemic inflammation, which results in organ injury. Toll-like Receptor 4 (TLR4)-signaling activation contributes to the initiation of inflammatory pathways following HS/T but its cell-specific roles in this setting are not known. We assessed the importance of TLR4 on leukocytes of myeloid lineage and dendritic cells (DCs) to the early systemic inflammatory response following HS/T. Mice were subjected to HS/T and 20 inflammatory mediators were measured in plasma followed by Dynamic Bayesian Network (DBN) Analysis. Organ damage was assessed by histology and plasma ALT levels. The role of TLR4 was determined using TLR4−/−, MyD88−/−, and Trif−/− C57BL/6 (B6) mice, and by in vivo administration of a TLR4-specific neutralizing monoclonal antibody (mAb). The contribution of TLR4 expressed by myeloid leukocytes and DC was determined by generating cell-specific TLR4−/− B6 mice, including Lyz-Cre × TLR4loxP/loxP, and CD11c-Cre × TLR4loxP/loxP B6 mice. Adoptive transfer of bone marrow-derived TLR4+/+ or TLR4−/− DC into TLR4−/− mice confirmed the contribution of TLR4 on DC to the systemic inflammatory response after HS/T. Using both global knockout mice and the TLR4-blocking mAb 1A6 we established a central role for TLR4 in driving systemic inflammation. Using cell-selective TLR4−/− B6 mice, we found that TLR4 expression on both myeloid cells and CD11chigh DC is required for increases in systemic cytokine levels and organ damage after HS/T. We confirmed the capacity of TLR4 on CD11chigh DC to promote inflammation and liver damage using adoptive transfer of TLR4+/+ conventional (CD11chigh) DC into TLR4−/− mice. DBN inference identified CXC chemokines as proximal drivers of dynamic changes in the circulating levels of cytokines/chemokines after HS/T. TLR4 on DC was found to contribute selectively to the elevations in these proximal drivers. TLR4 on both myeloid cells and conventional DC is required for the initial systemic inflammation and organ damage in a mouse model of HS/T. This includes a role for TLR4 on DC in promoting increases in the early inflammatory networks identified in HS/T. These data establish DC along with macrophages as essential to the recognition of tissue damage and stress following tissue trauma with HS