Alum interaction with dendritic cell membrane lipids is essential for its adjuvanticity.

As an approved vaccine adjuvant for use in humans, alum has vast health implications, but, as it is a crystal, questions remain regarding its mechanism. Furthermore, little is known about the target cells, receptors, and signaling pathways engaged by alum. Here we report that, independent of inflammasome and membrane proteins, alum binds dendritic cell (DC) plasma membrane lipids with substantial force.

Receptor-independent, direct membrane binding leads to cell-surface lipid sorting and Syk kinase activation in dendritic cells.

Binding of particulate antigens by antigen-presenting cells is a critical step in immune activation. Previously, we demonstrated that uric acid crystals are potent adjuvants, initiating a robust adaptive immune response. However, the mechanisms of activation are unknown.

Gene expression response in target organ and whole blood varies as a function of target organ injury phenotype.

This report details the standardized experimental design and the different data streams that were collected (histopathology, clinical chemistry, hematology and gene expression from the target tissue (liver) and a bio-available tissue (blood)) after treatment with eight known hepatotoxicants (at multiple time points and doses with multiple biological replicates). The results of the study demonstrate the classification of histopathological differences, likely reflecting differences in mechanisms of cell-specific toxicity, using either liver tissue or blood transcriptomic data.

Age and dose sensitivities in the 2-butoxyethanol F344 rat model of hemolytic anemia and disseminated thrombosis.

In hemolytic disorders, such as sickle cell disease and beta-thalassemia, the mechanisms of thrombosis are poorly understood. Appropriate animal models would increase the understanding of the pathophysiology of thrombosis. We previously reported that rats exposed to 2-butoxyethanol (2-BE) developed hemolytic anemia and disseminated thrombosis resembling sickle cell disease and beta-thalassemia.

Hemostatic activation in a chemically induced rat model of severe hemolysis and thrombosis.

Introduction: In hemolytic diseases such as sickle cell disease and beta-thalassemia, the mechanisms of thrombosis are poorly understood, however erythrocyte/endothelium interactions are thought to play an important role. Appropriate animal models would increase our understanding of the pathophysiology of thrombosis and aid in the development of new therapeutic strategies. We previously reported that rats exposed to 2-butoxyethanol (2-BE) develop hemolysis and enhanced adherence of erythrocytes to the extracellular matrix, possibly secondary to the recruitment of cellular adhesion molecules at the erythrocyte/endothelium interface.

Differential gene expression profiling in whole blood during acute systemic inflammation in lipopolysaccharide-treated rats.

Microarrays have been used to evaluate the expression of thousands of genes in various tissues. However, few studies have investigated the change in gene expression profiles in one of the most easily accessible tissues, whole blood. We utilized an acute inflammation model to investigate the possibility of using a cDNA microarray to measure the gene expression profile in the cells of whole blood.