title: Effects of human plasma proteins on maturation of monocyte-derived dendritic cells.
abstract: Dendritic cells (DC) are a promising tool for vaccine therapy due to their unique properties as antigen presenting cells and their ability to prime naïve T cells. Increasing evidence suggests that maturation stage of DC critically influences the fate of the immune response. Generation of monocyte-derived DC for clinically applicable immunotherapy requires the use of well-defined components and stringent culture conditions. An alternative strategy is to use human autologous serum. However, its constituents are not stable and reflect the inflammatory condition of the donor. In order to investigate whether DC properties are influenced by proteins present in the plasma, we matured human monocyte-derived DC with four main plasma components: fibrinogen, fibronectin, plasminogen or C-reactive protein. These purified proteins were added at various concentrations on day 6 after the initial differentiation induced by IL-4 and GM-CSF. The maturation was assessed by phenotyping of maturation-associated marker (CD83) and co-stimulatory molecule CD86 as well as IL-12 production. Functional properties of DC were assessed by endocytic activity and mixed leukocyte culture. Our results indicate that fibrinogen had DC-maturation effect comparable to poly-I:C, TNF-alpha and PGE(2) as a positive control, but it failed to induce IL-12 production. The other plasma proteins had no effect on DC maturation. CRP at high concentration had rather inhibitory effect on DC induced lymphocyte function. We conclude that none of the tested plasma components and acute phase proteins sufficiently induce fully competent mature DC. This finding is important for the preparation of human DC-based vaccines supplemented by autologous sera.
authors.affiliation: Department of Immunology, 2nd Medical Faculty and Faculty Hospital Motol, V Uvalu 84, 156 00 Prague 5, Czech Republic.
authors.forename: Z
authors.initials: Z
authors.lastname: Tobiásová-Czetoová
authors.forename: A
authors.initials: A
authors.lastname: Palmborg
authors.forename: A
authors.initials: A
authors.lastname: Lundqvist
authors.forename: G
authors.initials: G
authors.lastname: Karlsson
authors.forename: L
authors.initials: L
authors.lastname: Adamson
authors.forename: J
authors.initials: J
authors.lastname: Bartůnková
authors.forename: G
authors.initials: G
authors.lastname: Masucci
authors.forename: P
authors.initials: P
authors.lastname: Pisa
mesh_terms: D015703:Antigens, CD / Q000032:analysis; D001798:Blood Proteins / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D005340:Fibrinogen / Q000494:pharmacology; D006801:Humans; D007136:Immunoglobulins / Q000032:analysis; D016130:Immunophenotyping; D007959:Lymphocyte Culture Test, Mixed; D008545:Melanoma / Q000097:blood; D008562:Membrane Glycoproteins / Q000032:analysis; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology; D000097802:CD83 Antigen
chemical_list: D015703:Antigens, CD; D001798:Blood Proteins; D005340:Fibrinogen; D007136:Immunoglobulins; D008562:Membrane Glycoproteins; D000097802:CD83 Antigen