title: Low production of reactive oxygen species in granulocytes is associated with organ damage in systemic lupus erythematosus.
abstract: BACKGROUND
  Polymorphonuclear leukocytes (PMN) are main effector cells in the acute immune response. While the specific role of PMN in systemic lupus erythematosus (SLE) and autoimmunity is still unclear, their importance in chronic inflammation is gaining more attention. Here we investigate aspects of function, bone marrow release and activation of PMN in patients with SLE.
  
  
  METHODS
  The following PMN functions and subsets were evaluated using flow cytometry; (a) production of reactive oxygen species (ROS) after ex vivo stimulation with phorbol 12-myristate 13-acetate (PMA) or Escherichia coli (E. coli); (b) capacity to phagocytose antibody-coated necrotic cell material; (c) PMN recently released from bone marrow, defined as percentage of CD10(-)D16(low) in peripheral blood, and (d) PMN activation markers; CD11b, CD62L and C5aR.
  
  
  RESULTS
  SLE patients (n = 92) showed lower ROS production compared with healthy controls (n = 38) after activation ex vivo. The ROS production was not associated with corticosteroid dose or other immunotherapies. PMA induced ROS production was significantly reduced in patients with severe disease. In contrast, neither ROS levels after E. coli activation, nor the capacity to phagocytose were associated with disease severity. This suggests that decreased ROS production after PMA activation is a sign of changed PMN behaviour rather than generally impaired functions. The CD10(-)CD16(low) phenotype constitute 2% of PMN in peripheral blood of SLE patients compared with 6.4% in controls, indicating a decreased release of PMN from the bone marrow in SLE. A decreased expression of C5aR on PMN was observed in SLE patients, pointing towards in vivo activation.
  
  
  CONCLUSIONS
  Our results indicate that PMN from SLE patients have altered function, are partly activated and are released abnormally from bone marrow. The association between low ROS formation in PMN and disease severity is consistent with findings in other autoimmune diseases and might be considered as a risk factor.
authors.forename: Anders A
authors.initials: AA
authors.lastname: Bengtsson
authors.forename: Åsa
authors.initials: Å
authors.lastname: Pettersson
authors.forename: Stina
authors.initials: S
authors.lastname: Wichert
authors.forename: Birgitta
authors.initials: B
authors.lastname: Gullstrand
authors.forename: Markus
authors.initials: M
authors.lastname: Hansson
authors.forename: Thomas
authors.initials: T
authors.lastname: Hellmark
authors.forename: Åsa C M
authors.initials: ÅC
authors.lastname: Johansson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D039481:CD11b Antigen / Q000097:blood / Q000276:immunology; D004926:Escherichia coli / Q000276:immunology; D005434:Flow Cytometry; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D019041:L-Selectin / Q000097:blood / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000276:immunology* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000097:blood / Q000276:immunology*; D015260:Neprilysin / Q000097:blood / Q000276:immunology; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D010587:Phagocytosis / Q000276:immunology; D017382:Reactive Oxygen Species / Q000097:blood / Q000276:immunology*; D044087:Receptor, Anaphylatoxin C5a / Q000097:blood / Q000276:immunology; D017452:Receptors, IgG / Q000097:blood / Q000276:immunology; D013755:Tetradecanoylphorbol Acetate / Q000276:immunology / Q000494:pharmacology; D055815:Young Adult
chemical_list: D039481:CD11b Antigen; D017382:Reactive Oxygen Species; D044087:Receptor, Anaphylatoxin C5a; D017452:Receptors, IgG; D019041:L-Selectin; D015260:Neprilysin; D013755:Tetradecanoylphorbol Acetate