title: Apoptotic-cell-derived membrane microparticles and IFN-α induce an inflammatory immune response.
abstract: A dysregulation in the clearance of apoptotic material is considered a major pathogenetic factor for the emergence of autoimmune diseases. Apoptotic-cell-derived membrane microparticles (AdMPs), which are released from the cell surface during apoptosis, have been implicated in the pathogenesis of autoimmunity. Also of importance are cytokines, such as interferon-α (IFN-α), which is known to be a major player in patients with systemic lupus erythematosus (SLE). This study investigates the combined effect of AdMPs and IFN-α on professional phagocytes. In the presence of IFN-α, phagocytosis of AdMPs by human monocytes was significantly increased in a dose-dependent manner. The combination of AdMPs and raised IFN-α concentrations resulted in an increase in the secretion of pro-inflammatory cytokines and an upregulation of surface molecule expression involved in antigen uptake. In addition, macrophage polarisation was shifted towards a more inflammatory type of cell. The synergism between IFN-α and AdMPs seemed to be mediated by an upregulation of phosphorylated STAT1. Our results indicate that IFN-α, together with AdMPs, amplify the initiation and maintenance of inflammation. This mechanism might especially play a crucial role in disorders with a defective clearance of apoptotic material.
authors.affiliation: Department of Internal Medicine V, Division of Rheumatology, University Hospital Heidelberg, Heidelberg 69120, Germany anna.niessen@med.uni-heidelberg.de.
authors.forename: Anna
authors.initials: A
authors.lastname: Niessen
authors.affiliation: Department of Internal Medicine V, Division of Rheumatology, University Hospital Heidelberg, Heidelberg 69120, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Heyder
authors.affiliation: Department of Internal Medicine V, Division of Rheumatology, University Hospital Heidelberg, Heidelberg 69120, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Krienke
authors.affiliation: Department of Internal Medicine V, Division of Rheumatology, University Hospital Heidelberg, Heidelberg 69120, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Blank
authors.affiliation: Department of Internal Medicine V, Division of Rheumatology, University Hospital Heidelberg, Heidelberg 69120, Germany.
authors.forename: Lars-Oliver
authors.initials: LO
authors.lastname: Tykocinski
authors.affiliation: Department of Internal Medicine V, Division of Rheumatology, University Hospital Heidelberg, Heidelberg 69120, Germany.
authors.forename: Hanns-Martin
authors.initials: HM
authors.lastname: Lorenz
authors.affiliation: Department of Internal Medicine V, Division of Rheumatology, University Hospital Heidelberg, Heidelberg 69120, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Schiller
mesh_terms: D017209:Apoptosis / Q000276:immunology*; D055252:Cell-Derived Microparticles / Q000276:immunology* / Q000473:pathology; D005260:Female; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D016898:Interferon-alpha / Q000276:immunology*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000473:pathology; D008264:Macrophages / Q000276:immunology* / Q000473:pathology; D008297:Male; D050794:STAT1 Transcription Factor / Q000276:immunology
chemical_list: D016898:Interferon-alpha; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human
keywords: Apoptosis; Cell blebbing; Clearance; Interferon-α; Membrane microparticle; Systemic lupus erythematosus