title: Heat shock protein 70 is a potent activator of the human complement system.
abstract: According to new hypotheses, extracellular heat shock proteins (Hsps) may represent an ancestral danger signal of cellular death or lysis-activating innate immunity. Recent studies demonstrating a dual role for Hsp70 as both a chaperone and cytokine, inducing potent proinflammatory response in human monocytes, provided support for the hypothesis that extracellular Hsp is a messenger of stress. Our previous work focused on the complement-activating ability of human Hsp60. We demonstrated that Hsp60 complexed with specific antibodies induces a strong classical pathway (CP) activation. Here, we show that another chaperone molecule also possesses complement-activating ability. Solid-phase enzyme-linked immunosorbent assay was applied for the experiments. Human Hsp70 activated the CP independently of antibodies. No complement activation was found in the case of human Hsp90. Our data further support the hypothesis that chaperones may messenger stress to other cells. Complement-like molecules and primitive immune cells appeared together early in evolution. A joint action of these arms of innate immunity in response to free chaperones, the most abundant cellular proteins displaying a stress signal, may further strengthen the effectiveness of immune reactions.
authors.affiliation: 3rd Department of Internal Medicine, Faculty of Medicine, Semmelweis University, Budapest, Hungary. prohoz@kut.sote.hu
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Prohászka
authors.forename: Mahavir
authors.initials: M
authors.lastname: Singh
authors.forename: Kálmán
authors.initials: K
authors.lastname: Nagy
authors.forename: Emese
authors.initials: E
authors.lastname: Kiss
authors.forename: Gabriella
authors.initials: G
authors.lastname: Lakos
authors.forename: Jenö
authors.initials: J
authors.lastname: Duba
authors.forename: George
authors.initials: G
authors.lastname: Füst
mesh_terms: D003171:Complement Pathway, Classical / Q000502:physiology*; D003165:Complement System Proteins / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged
chemical_list: D018840:HSP70 Heat-Shock Proteins; D003165:Complement System Proteins