title: Immunostimulation by bacterial components: I. Activation Of macrophages and enhancement of genetic immunization by the lipopeptide P3CSK4.
abstract: Synthetic lipopeptides derived from the N-terminus of bacterial lipoprotein constitute potent macrophage activators and polyclonal B-lymphocyte stimulators. They are also efficient immunoadjuvants in parenteral, oral and nasal immunization either in combination with or after covalent linkage to an antigen. Here we show how alterations in the molecular structure influence their biological properties indicating P3CSK4 as one of the most active members of a lipopentapeptide fatty acid library. This compound resulted in a most pronounced macrophage stimulation as indicated by NO release, activation of NFkappaB translocation, and enhancement of tyrosine protein phosphorylation. Furthermore, P3CSK4 activates/represses an array of at least 140 genes partly involved in signal transduction and regulation of the immune response. Finally we have evidence that P3CSK4 constitutes an effective adjuvant for DNA immunizations, especially increasing weak humoral immune responses. Our findings are of importance for further optimizing both conventional and genetic immunization, and for the development of novel synthetic vaccines.
authors.affiliation: Institut für Molekulare Medizin und Zellforschung der Universität Freiburg, AK Tumorimmunologie/Vakzine, Stefan-Meier-Str. 8, D-79104, Freiburg, Germany.
authors.forename: U
authors.initials: U
authors.lastname: vd Esche
authors.forename: M
authors.initials: M
authors.lastname: Ayoub
authors.forename: S D
authors.initials: SD
authors.lastname: Pfannes
authors.forename: M R
authors.initials: MR
authors.lastname: Müller
authors.forename: M
authors.initials: M
authors.lastname: Huber
authors.forename: K H
authors.initials: KH
authors.lastname: Wiesmüller
authors.forename: T
authors.initials: T
authors.lastname: Loop
authors.forename: M
authors.initials: M
authors.lastname: Humar
authors.forename: K F
authors.initials: KF
authors.lastname: Fischbach
authors.forename: M
authors.initials: M
authors.lastname: Strünkelnberg
authors.forename: P
authors.initials: P
authors.lastname: Hoffmann
authors.forename: W G
authors.initials: WG
authors.lastname: Bessler
authors.forename: K
authors.initials: K
authors.lastname: Mittenbühler
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000906:Antibodies / Q000032:analysis; D001419:Bacteria / Q000737:chemistry*; D004247:DNA / Q000187:drug effects / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007109:Immunity / Q000187:drug effects / Q000235:genetics*; D066298:In Vitro Techniques; D008074:Lipoproteins / Q000494:pharmacology*; D008262:Macrophage Activation / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D016328:NF-kappa B / Q000276:immunology; D009569:Nitric Oxide / Q000378:metabolism; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism
chemical_list: D000276:Adjuvants, Immunologic; D000906:Antibodies; D008074:Lipoproteins; D016328:NF-kappa B; C061108:N-palmitoyl-S-(2,3-bis(palmitoyloxy)propyl)cysteinyl-seryl-lysyl-lysyl-lysyl-lysine; D009569:Nitric Oxide; D004247:DNA; D011505:Protein-Tyrosine Kinases