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The adjuvants aluminum hydroxide and MF59 induce monocyte and granulocyte chemoattractants and enhance monocyte differentiation toward dendritic cells.
The adjuvants aluminum hydroxide and MF59 induce monocyte and granulocyte chemoattractants and enhance monocyte differentiation toward dendritic cells.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2008 Apr 15; Vol. 180 (8), pp. 5402-12. - Publication Year :
- 2008
-
Abstract
- Aluminum hydroxide (alum) and the oil-in-water emulsion MF59 are widely used, safe and effective adjuvants, yet their mechanism of action is poorly understood. We assessed the effects of alum and MF59 on human immune cells and found that both induce secretion of chemokines, such as CCL2 (MCP-1), CCL3 (MIP-1alpha), CCL4 (MIP-1beta), and CXCL8 (IL-8), all involved in cell recruitment from blood into peripheral tissue. Alum appears to act mainly on macrophages and monocytes, whereas MF59 additionally targets granulocytes. Accordingly, monocytes and granulocytes migrate toward MF59-conditioned culture supernatants. In monocytes, both adjuvants lead to increased endocytosis, enhanced surface expression of MHC class II and CD86, and down-regulation of the monocyte marker CD14, which are all phenotypic changes consistent with a differentiation toward dendritic cells (DCs). When monocyte differentiation into DCs is induced by addition of cytokines, these adjuvants enhanced the acquisition of a mature DC phenotype and lead to an earlier and higher expression of MHC class II and CD86. In addition, MF59 induces further up-regulation of the maturation marker CD83 and the lymph node-homing receptor CCR7 on differentiating monocytes. Alum induces a similar but not identical pattern that clearly differs from the response to LPS. This model suggests a common adjuvant mechanism that is distinct from that mediated by danger signals. We conclude that during vaccination, adjuvants such as MF59 may increase recruitment of immune cells into the injection site, accelerate and enhance monocyte differentiation into DCs, augment Ag uptake, and facilitate migration of DCs into tissue-draining lymph nodes to prime adaptive immune responses.
- Subjects :
- B7-2 Antigen immunology
B7-2 Antigen metabolism
Cell Differentiation
Chemokines, CC immunology
Dendritic Cells cytology
Dendritic Cells drug effects
Endocytosis
Granulocytes drug effects
Granulocytes metabolism
Histocompatibility Antigens Class II immunology
Histocompatibility Antigens Class II metabolism
Humans
Lipopolysaccharide Receptors immunology
Lipopolysaccharide Receptors metabolism
Monocytes cytology
Monocytes drug effects
Polysorbates
Adjuvants, Immunologic
Aluminum Hydroxide immunology
Chemokines, CC metabolism
Dendritic Cells immunology
Granulocytes immunology
Monocytes immunology
Squalene immunology
Subjects
Details
- Language :
- English
- ISSN :
- 0022-1767
- Volume :
- 180
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 18390722
- Full Text :
- https://doi.org/10.4049/jimmunol.180.8.5402