Apoptotic cell-derived membrane microparticles and IFN-α induce an inflammatory immune response

Abstract

The dysregulation in clearance of apoptotic material is considered a major pathogenetic factor for the emergence of autoimmune diseases. Apoptotic cell-derived membrane microparticles (AdMPs), released from the cell surface during apoptosis, have been implicated in the pathogenesis of autoimmunity. Also of importance are cytokines such as interferon-alpha (IFN-α), known as 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. Also, macrophage polarisation was shifted towards a more inflammatory type of cell. The synergism between IFN-α and AdMPs seems 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. Especially in disorders with a defective clearance of apoptotic material, this mechanism might play a crucial role.