title: Improved stimulation of human dendritic cells by receptor engagement with surface-modified microparticles.
abstract: Dendritic cells (DC) need to be stimulated before they can function to initiate immune responses. This study investigates whether microparticles loaded with antibodies specific for selected receptors expressed by DC can induce stimulation of these cells. Plain microparticles were compared with microparticles which were surface-loaded with specific antibodies for human CD40, Fc(gamma), alpha(v)beta3 and alpha(v)beta5 integrin receptors. The antibodies were either physically adsorbed or covalently linked to the microparticle surface. Anti-CD40 antibody and human IgG immobilised on the surface of microparticles induced enhanced DC maturation and activation as expressed by CD83 and CD86 upregulation. IL-12 secretion was induced at a detectable but relatively low level. Both anti-integrin antibodies (anti-alpha(v)beta3 and anti-alpha(v)beta5) induced comparable and considerable maturation of DC, but only anti-alpha(v)beta3 antibody induced significant activation of DC, whereas anti-alpha(v)beta5 did not. The stimulatory effects were most pronounced by employing microparticles with covalently linked antibodies, but were also observed to a minor extent when the antibodies were physically adsorbed to polystyrene and biodegradable poly(lactide-co-glycolide) microparticles. Engineering of microparticles by surface conjugation of specific ligands to stimulate DC may increase the effectiveness of microparticulate vaccine delivery systems.
authors.affiliation: Department of Applied BioSciences, Drug Formulation & Delivery Group, Swiss Federal Institute of Technology Zurich (ETH), Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.
authors.forename: Martina
authors.initials: M
authors.lastname: Kempf
authors.forename: Barnali
authors.initials: B
authors.lastname: Mandal
authors.forename: Samantha
authors.initials: S
authors.lastname: Jilek
authors.forename: Lars
authors.initials: L
authors.lastname: Thiele
authors.forename: Janos
authors.initials: J
authors.lastname: Vörös
authors.forename: Markus
authors.initials: M
authors.lastname: Textor
authors.forename: Hans P
authors.initials: HP
authors.lastname: Merkle
authors.forename: Elke
authors.initials: E
authors.lastname: Walter
mesh_terms: D000954:Antigens, Surface / Q000276:immunology / Q000378:metabolism*; D002214:Capsules; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D019344:Lactic Acid / Q000008:administration & dosage; D011100:Polyglycolic Acid / Q000008:administration & dosage; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000008:administration & dosage; D011956:Receptors, Cell Surface / Q000276:immunology / Q000378:metabolism*
chemical_list: D000954:Antigens, Surface; D002214:Capsules; D011108:Polymers; D011956:Receptors, Cell Surface; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid