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.

journal_name

J Cell Sci

journal_title

Journal of cell science

authors

Niessen A,Heyder P,Krienke S,Blank N,Tykocinski LO,Lorenz HM,Schiller M

doi

10.1242/jcs.162735

subject

Has Abstract

pub_date

2015-07-15 00:00:00

pages

2443-53

issue

14

eissn

0021-9533

issn

1477-9137

pii

jcs.162735

journal_volume

128

pub_type

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