title: Remnants of secondarily necrotic cells fuel inflammation in systemic lupus erythematosus.
abstract: OBJECTIVE
  Patients with systemic lupus erythematosus (SLE) are often characterized by cellular as well as humoral deficiencies in the recognition and phagocytosis of dead and dying cells. The aim of this study was to investigate whether the remnants of apoptotic cells are involved in the induction of inflammatory cytokines in blood-borne phagocytes.
  
  
  METHODS
  We used ex vivo phagocytosis assays comprising cellular and humoral components and phagocytosis assays with isolated granulocytes and monocytes to study the phagocytosis of secondarily necrotic cell-derived material (SNEC). Cytokines were measured by multiplex bead array technology.
  
  
  RESULTS
  We confirmed the impaired uptake of various particulate targets, including immunoglobulin-opsonized beads, by granulocytes and monocytes from patients with SLE compared with healthy control subjects. Surprisingly, blood-borne phagocytes from two-thirds of the patients with SLE took up SNEC, which was rarely phagocytosed by phagocytes from healthy control subjects or patients with rheumatoid arthritis. Supplementation of healthy donor blood with IgG fractions derived from patients with SLE transferred the capability to take up SNEC to the phagocytes of healthy donors. Phagocytosis-promoting immune globulins also induced secretion of huge amounts of cytokines by blood-borne phagocytes following uptake of SNEC.
  
  
  CONCLUSIONS
  Opsonization of SNEC by autoantibodies from patients with SLE fosters its uptake by blood-borne monocytes and granulocytes. Autoantibody-mediated phagocytosis of SNEC is accompanied by secretion of inflammatory cytokines, fueling the inflammation that contributes to the perpetuation of autoimmunity in SLE.
authors.affiliation: University Hospital of Erlangen, Department of Radiation Oncology, Friedrich-Alexander University of Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Luis E
authors.initials: LE
authors.lastname: Muñoz
authors.forename: Christina
authors.initials: C
authors.lastname: Janko
authors.forename: Gerhard E
authors.initials: GE
authors.lastname: Grossmayer
authors.forename: Benjamin
authors.initials: B
authors.lastname: Frey
authors.forename: Reinhard E
authors.initials: RE
authors.lastname: Voll
authors.forename: Peter
authors.initials: P
authors.lastname: Kern
authors.forename: Joachim R
authors.initials: JR
authors.lastname: Kalden
authors.forename: Georg
authors.initials: G
authors.lastname: Schett
authors.forename: Rainer
authors.initials: R
authors.lastname: Fietkau
authors.forename: Martin
authors.initials: M
authors.lastname: Herrmann
authors.forename: Udo S
authors.initials: US
authors.lastname: Gaipl
mesh_terms: D000328:Adult; D000368:Aged; D000888:Antibodies, Anti-Idiotypic / Q000378:metabolism; D017209:Apoptosis / Q000502:physiology*; D016022:Case-Control Studies; D016207:Cytokines / Q000378:metabolism; D004247:DNA / Q000276:immunology; D005260:Female; D006098:Granulocytes / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D008180:Lupus Erythematosus, Systemic / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism / Q000473:pathology; D009336:Necrosis / Q000503:physiopathology; D010586:Phagocytes / Q000378:metabolism / Q000473:pathology; D010587:Phagocytosis / Q000502:physiology
chemical_list: D000888:Antibodies, Anti-Idiotypic; D016207:Cytokines; D007074:Immunoglobulin G; D004247:DNA