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Low production of reactive oxygen species in granulocytes is associated with organ damage in systemic lupus erythematosus

Bengtsson, Anders LU ; Pettersson, Åsa LU ; Wichert, Stina LU ; Gullstrand, Birgitta LU ; Hansson, Markus LU ; Hellmark, Thomas LU and Johansson, Åsa LU (2014) In Arthritis Research and Therapy 16(3).
Abstract
Introduction: 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... (More)
Introduction: 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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Arthritis Research and Therapy
volume
16
issue
3
publisher
BioMed Central
external identifiers
  • wos:000347078700015
  • scopus:84903134145
ISSN
1478-6362
DOI
10.1186/ar4575
language
English
LU publication?
yes
id
a556f053-27dc-465a-8987-f38c619952ea (old id 5091494)
date added to LUP
2015-03-02 07:13:59
date last changed
2017-10-29 03:13:08
@article{a556f053-27dc-465a-8987-f38c619952ea,
  abstract     = {Introduction: 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.},
  articleno    = {R120},
  author       = {Bengtsson, Anders and Pettersson, Åsa and Wichert, Stina and Gullstrand, Birgitta and Hansson, Markus and Hellmark, Thomas and Johansson, Åsa},
  issn         = {1478-6362},
  language     = {eng},
  number       = {3},
  publisher    = {BioMed Central},
  series       = {Arthritis Research and Therapy},
  title        = {Low production of reactive oxygen species in granulocytes is associated with organ damage in systemic lupus erythematosus},
  url          = {http://dx.doi.org/10.1186/ar4575},
  volume       = {16},
  year         = {2014},
}