Endothelial activation and injury by microparticles in patients with systemic lupus erythematosus and rheumatoid arthritis

Abstract

Background Endothelial activation and damage is commonly observed in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) and is related to development of atherosclerosis and cardiovascular diseases. Different components of the immune system seem to participate in the endothelial injury, such as generation of autoantibodies and formation of immune complexes (ICs). Microparticles (MPs) and their immune complexes (MPs-ICs) are increased in the circulation of patients with SLE and RA; therefore, we propose these extracellular vesicles could interact and modulate the function of endothelial cells. Hence, the effect of MPs and MPs-ICs from patients with SLE and RA in endothelial cells was evaluated. Methods Macrovascular and microvascular endothelial cells were exposed to MPs and MPs-ICs from healthy donors and patients with SLE and RA. Vesicles uptake/binding, expression of adhesion molecules, cytokine and chemokine production, monocyte adherence, and alterations of endothelial monolayer were evaluated by flow cytometry and fluorescence microscopy. Results Endothelial cells internalized MPs and MPs-ICs and increased CD54 and CD102 expression and CCL2, CCL5, and IL-6 production after the treatment with these extracellular vesicles, which led to an increase in the adherence of classic monocytes. These vesicles also induced low expression of VE-cadherin in membrane, depolymerization of actin filaments, and formation of intercellular spaces, which led to endothelial death and increased permeability after MPs and MPs-ICs exposure. Conclusions MPs and MPs-ICs from patients with SLE and RA increase adhesion molecules expression, chemokine production, and structural alterations in macrovascular and microvascular endothelial cells. Therefore, high counts of these vesicles in patients would promote endothelial alterations and secondary tissue leukocyte infiltration. Electronic supplementary material The online version of this article (10.1186/s13075-018-1796-4) contains supplementary material, which is available to authorized users.

Lupus serum induces inflammatory interaction with neutrophils in human glomerular endothelial cells

“…Several reports suggest receptor-mediated and redox signalling mechanisms lead to endothelial dysfunction. [20][21][22][23][24][25][26] Our laboratory has published that eNOS is uncoupled with addition of lupus serum. 17 This uncoupling leads to production of reactive oxygen species in an animal model of LN and in LN glomerular tissue.…”

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 . Moreover, EVs derived from platelets mostly harbored IgG and overexpressed CD69 and CD64, and promoted pro-inflammatory responses in monocytes, thus exacerbating SLE-associated inflammation 190 .…”

“…Recent work from us and others has indicated that EVs play key immunomodulatory roles in the pathogenesis of various inflammatory skin diseases, such as psoriasis 11 , 12 , atopic dermatitis (AD) 13 , lichen planus (LP) 14 , bullous pemphigoid (BP) 15 , systemic lupus erythematosus (SLE) 16 , and chronic wound healing 7 . These inflammatory skin disorders pose major problems in dermatology given their complex pathophysiology and refractory nature, which ultimately pose a burden to the health, economic and social systems.…”

Complement Activation on Endothelial Cell-Derived Microparticles—A Key Determinant for Cardiovascular Risk in Patients with Systemic Lupus Erythematosus?

“…Platelet-derived microparticles generate thrombin, thereby aggravating hypercoagulability. Circulating microparticles, including those derived from endothelial cells, are novel biomarkers in SLE [ 17 ], but studies have not related these to clinical disease activity [ 3 , 18 , 19 , 20 ] or evaluated for cardiovascular risk in SLE the proportion of IgG-decorated microparticles that also fixed complement [ 21 ].…”