Apoptotic-cell-derived membrane microparticles and IFN-α induce an inflammatory immune response
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Apoptotic-cell-derived membrane microparticles and IFN-α induce an inflammatory immune response. / Nießen, Anna; Heyder, Petra; Krienke, Stefan; Blank, Norbert; Tykocinski, Lars-Oliver; Lorenz, Hanns-Martin; Schiller, Martin.
In: J CELL SCI, Vol. 128, No. 14, 15.07.2015, p. 2443-53.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Apoptotic-cell-derived membrane microparticles and IFN-α induce an inflammatory immune response
AU - Nießen, Anna
AU - Heyder, Petra
AU - Krienke, Stefan
AU - Blank, Norbert
AU - Tykocinski, Lars-Oliver
AU - Lorenz, Hanns-Martin
AU - Schiller, Martin
N1 - © 2015. Published by The Company of Biologists Ltd.
PY - 2015/7/15
Y1 - 2015/7/15
N2 - 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.
AB - 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.
KW - Apoptosis/immunology
KW - Cell-Derived Microparticles/immunology
KW - Female
KW - Humans
KW - Inflammation/immunology
KW - Interferon-alpha/immunology
KW - Lupus Erythematosus, Systemic/immunology
KW - Macrophages/immunology
KW - Male
KW - STAT1 Transcription Factor/immunology
U2 - 10.1242/jcs.162735
DO - 10.1242/jcs.162735
M3 - SCORING: Journal article
C2 - 26034070
VL - 128
SP - 2443
EP - 2453
JO - J CELL SCI
JF - J CELL SCI
SN - 0021-9533
IS - 14
ER -
