The Adjuvants Aluminum Hydroxide and MF59 Induce Monocyte and Granulocyte Chemoattractants and Enhance Monocyte Differentiation toward Dendritic Cells

摘要: Aluminum hydroxide (alum) and the oil-in-water emulsion MF59 are widely used, safe effective adjuvants, yet their mechanism of action is poorly understood. We assessed effects alum on human immune cells found that both induce secretion chemokines, such as CCL2 (MCP-1), CCL3 (MIP-1alpha), CCL4 (MIP-1beta), CXCL8 (IL-8), all involved in cell recruitment from blood into peripheral tissue. Alum appears to act mainly macrophages monocytes, whereas additionally targets granulocytes. Accordingly, monocytes granulocytes migrate toward MF59-conditioned culture supernatants. In adjuvants lead increased endocytosis, enhanced surface expression MHC class II CD86, down-regulation monocyte marker CD14, which phenotypic changes consistent with a differentiation dendritic (DCs). When DCs induced by addition cytokines, these acquisition mature DC phenotype an earlier higher CD86. addition, induces further up-regulation maturation CD83 lymph node-homing receptor CCR7 differentiating monocytes. similar but not identical pattern clearly differs response LPS. This model suggests common adjuvant distinct mediated danger signals. conclude during vaccination, may increase injection site, accelerate enhance DCs, augment Ag uptake, facilitate migration tissue-draining nodes prime adaptive responses.