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 dosedependent manner. The combination of AdMPs and raised IFN-α concentrations resulted in an increase in the secretion of proinflammatory 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.

Microparticles in the blood of patients with systemic lupus erythematosus (SLE): phenotypic characterization and clinical associations

“…TNFRs have also been associated with disease activity in SLE, in particular with active nephritis4950. Two recent in vitro studies have reported that particles can induce NETosis as well as the production of INF-α and other pro-inflammatory cytokines3851. Further studies are needed to understand how particles relate to the different phases of SLE activity.…”

Engulfment signals and the phagocytic machinery for apoptotic cell clearance

“…38 Recently, microparticles released from apoptotic cells have been shown to induce immune responses to apoptotic cell-derived antigens in the presence of IFN-α. 39 Chromatin on the apoptotic cell surface appears to be a self-antigen that triggers immunogenic responses. 40 Thus, microparticles elicited from apoptotic cells might be removed to maintain tissue homeostasis and prevent aberrant inflammation.…”

Microvesicles: Intercellular messengers in cutaneous wound healing

“…Certain factors have been shown to amplify MV internalization into monocytes/macrophages. Notably, Niessen et al () revealed that the uptake of MVs is dose‐dependently increased in the presence of IFN‐α, an effect mediated by upregulation of phosphorylated STAT1 in monocytes. Likewise, Litvack, Post, and Palaniyar () reported that opsonization of apoptotic cell‐derived MVs by IgM enhances phagocytosis by macrophages.…”