Dysregulation of Macrophage Activation Profiles by Engineered Nanoparticles

To investigate how the phenotype of macrophages that have engulfed engineered nanoparticles (ENPs) differs from normal macrophages, we conducted Affymetrix microarray studies to identify the gene regulatory pathways affected by the ENPs. To mimic potential occupational exposure scenarios, the experimental design involved pretreatment of mouse primary bone marrow macrophages with the ENPs (25 mg/ml) for 24 hr, followed by removal of residual ENPs and challenging the macrophages with the TLR4 ligand and surrogate bacterial stimulus, lipopolysachharide (LPS) for 4 hr. The 4 hr challenge time was chosen based on preliminary studies which showed many of the proinflammatory gene expression responses peak between 2-6 hr after LPS treatment.

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Kodali V, Littke MH, Tilton SC, Teeguarden JG, Shi L, Frevert CW, Wang W, Pounds JG, Thrall BD