Microparticles from patients with systemic lupus erythematosus induce production of reactive oxygen species and degranulation of polymorphonuclear leukocytes

Abstract

BackgroundThe interaction of circulating microparticles (MPs) with immune cells in systemic lupus erythematosus (SLE) is sparsely investigated. We examined the ability of MPs from SLE patients to induce production of reactive oxygen species (ROS) and degranulation of polymorphonuclear leukocytes (PMNs).MethodsPlasma MPs, leukocytes and sera isolated from 20 SLE patients and 10 healthy controls were mixed in different combinations, with or without lipopolysaccharide (LPS), and incubated for 30 min. Dihydrorhodamine 123 was used to measure ROS production by flow cytometry. The ability of immunoglobulin G (IgG) isolated from five SLE patients to increase MP-induced production of ROS by PMNs was tested. Cell supernatants were analysed for content of primary, secondary and tertiary granule components by Luminex assays.ResultsMPs from SLE patients promoted ROS production by PMNs, and enhanced LPS-induced ROS production and release of primary granules by PMNs, when added to samples of autologous leukocytes and serum. In a similar autologous setting, MPs from healthy controls enhanced LPS-induced ROS production by PMNs. When leukocytes from a healthy control were stimulated with autologous MPs in the presence of various sera, SLE patient serum promoted ROS production and release of primary and secondary granules by PMNs. A role for antibodies in this respect was indicated by the observation that supplementation of normal serum with IgG from SLE patients promoted MP-induced ROS production by healthy PMNs. Moreover, when various MPs were incubated with leukocytes and serum from a healthy control, patient-derived MPs induced more ROS production by PMNs than did healthy control-derived MPs.ConclusionsSLE patients display increased ROS production and degranulation by PMNs in response to MPs, which partly depends on serum components, including antibodies, MP properties and hyper-responsiveness of the PMNs per se.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-017-1437-3) contains supplementary material, which is available to authorized users.

Microvesicles: ROS scavengers and ROS producers

“…Similar results have been reported for MVs derived from cells subjected to stress or under pathological conditions. MVs derived from ischemic muscles (56), plasma of patients with lupus [99] or neutrophils infected with Mycobacterium tuberculosis [70] were shown to induce ROS in mononuclear cells, neutrophils and macrophages, respectively. However, MVs derived from cells exposed to ROS induced ROS tolerance in PC12 cells [100].…”

Extracellular vesicles in Inflammatory Skin Disorders: from Pathophysiology to Treatment

“…Moreover, it was shown that these increased EVs in the plasma of active SLE patients induced ROS production and degranulation in neutrophils 187 , activated pDCs to secrete IFN-α via TLR7 188 , or contributed to MSC senescence in SLE 189 . The elevated EVs and their immune complexes in SLE patients also promoted secondary leukocyte infiltration by regulating vascular remodeling and chemokine secretion 16 .…”

Exosomes as Drug Delivery Systems: Endogenous Nanovehicles for Treatment of Systemic Lupus Erythematosus

“…Dieker et al reported that circulating apoptotic MPs from SLE patients drive the activation of dendritic cell subsets and prime neutrophils [ 74 ]. In another study, Winber et al demonstrated that SLE patients display increased ROS production and degranulation by polymorphonuclear leukocytes (PMNs) in response to MPs [ 75 ]. Recently, Burbano et al highlighted the involvement of platelet-derived MPs during monocyte activation in patients with SLE, showing that MPs are one of the most representative sources of the total amount of circulating ICs-IgG + in patients with SLE [ 76 ].…”