title: Different efficiency of heat shock proteins (HSP) to activate human monocytes and dendritic cells: superiority of HSP60.
abstract: One essential immunoregulatory function of heat shock protein (HSP) is activation of the innate immune system. We investigated the activation of human monocytes and monocyte-derived dendritic cells (DC) by recombinant human HSP60, human inducible HSP72, and preparations of human gp96 and HSP70 under stringent conditions, in the absence of serum and with highly purified monocytes. HSP60 induced human DC maturation and activated human DC to secrete proinflammatory cytokines. HSP72 induced DC maturation to a lesser extent, but activated human monocytes and immature DC as efficiently as HSP60 to release proinflammatory cytokines. The independence of the effects of HSP60 and HSP72 from endotoxin or another copurifying bacterial component was shown by the resistance of these effects to polymyxin B, their sensitivity to heat treatment, the inactivity of endotoxin controls at concentrations up to 100-fold above the endotoxin contents of the HSP, and the inactivity of a recombinant control protein. Preparations of HSP70, which consisted mainly of the constitutively expressed HSP73, induced only marginal cytokine release from monocytes. The gp96 preparations did not have significant effects on human monocytes and monocyte-derived DC, indicating that these human APC populations were not susceptible to gp96 signaling under the stringent conditions applied in this study. The biological activities of gp96 and HSP70 preparations were confirmed by their peptide binding activity. These findings show that HSP can differ considerably in the capacity to activate monocyte-derived APC under certain conditions and underline the potential of HSP60 and HSP72 as activation signals for the innate immune system.
authors.affiliation: First Department of Internal Medicine and Department of Dermatology, Johannes Gutenberg Universität, Mainz, Germany.
authors.forename: Karen
authors.initials: K
authors.lastname: Bethke
authors.forename: Frank
authors.initials: F
authors.lastname: Staib
authors.forename: Martin
authors.initials: M
authors.lastname: Distler
authors.forename: Ute
authors.initials: U
authors.lastname: Schmitt
authors.forename: Helmut
authors.initials: H
authors.lastname: Jonuleit
authors.forename: Alexander H
authors.initials: AH
authors.lastname: Enk
authors.forename: Peter R
authors.initials: PR
authors.lastname: Galle
authors.forename: Michael
authors.initials: M
authors.lastname: Heike
mesh_terms: D000951:Antigens, Neoplasm / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D018834:Chaperonin 60 / Q000494:pharmacology*; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology*; D018840:HSP70 Heat-Shock Proteins / Q000494:pharmacology; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000494:pharmacology*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008213:Lymphocyte Activation; D009000:Monocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology*; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000951:Antigens, Neoplasm; D018834:Chaperonin 60; D016207:Cytokines; D018840:HSP70 Heat-Shock Proteins; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D018836:Inflammation Mediators; D011994:Recombinant Proteins; C052646:sarcoma glycoprotein gp96 rejection antigens