title: Mycobacterial heat-shock protein 65 induces proinflammatory cytokines but does not activate human mononuclear phagocytes.
abstract: The 65 kDa heat-shock protein (Hsp65), a well-conserved and immunodominant antigen which elicits a cellular and humoral immune response, may play a role in host defence against invading microorganisms and autoimmune disorders. The aim of the present study was to assess the effects of Hsp65 on the functional activities of human mononuclear phagocytes in the absence of lymphocytes. Incubation with Hsp65 resulted in an enhanced release of TNF-alpha and IL-1 beta by human monocytes and monocyte-derived macrophages (MDM). The amount of cytokines released by these cells in response to Hsp65 was similar to that released in response to IFN-gamma together with LPS. Incubation with ovalbumin did not stimulate the release of these cytokines. In vitro stimulation of monocytes with Hsp65 enhanced the membrane expression of complement receptor III but did not influence either the expression of Fc gamma-receptor I and HLA class-II antigens or the release of reactive oxygen intermediates. Therefore, Hsp65-stimulated monocytes cannot be considered to be activated according to classical criteria. The release of the proinflammatory cytokines TNF-alpha and IL-1 beta by human mononuclear phagocytes in response to Hsp65 indicates that this protein can contribute to both host defence and tissue damage in inflammatory lesions characterized by an abundant expression of Hsp65.
authors.affiliation: Department of Infectious Diseases, University Hospital Leiden, The Netherlands.
authors.forename: W E
authors.initials: WE
authors.lastname: Peetermans
authors.forename: C J
authors.initials: CJ
authors.lastname: Raats
authors.forename: J A
authors.initials: JA
authors.lastname: Langermans
authors.forename: R
authors.initials: R
authors.lastname: van Furth
mesh_terms: D000954:Antigens, Surface / Q000096:biosynthesis; D001426:Bacterial Proteins / Q000502:physiology*; D002478:Cells, Cultured; D018834:Chaperonin 60; D018833:Chaperonins; D016207:Cytokines / Q000096:biosynthesis*; D006360:Heat-Shock Proteins / Q000276:immunology*; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis; D008262:Macrophage Activation / Q000502:physiology*; D009000:Monocytes / Q000276:immunology*; D009163:Mycobacterium bovis / Q000276:immunology*; D013481:Superoxides / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D000954:Antigens, Surface; D001426:Bacterial Proteins; D018834:Chaperonin 60; D016207:Cytokines; D006360:Heat-Shock Proteins; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; C074119:heat-shock protein 65, Mycobacterium; D013481:Superoxides; D018833:Chaperonins