Original Research ARTICLE
POTENTIAL INVOLVEMENT OF PLATELET-DERIVED MICROPARTICLES AND MICROPARTICLES FORMING IMMUNE COMPLEXES DURING MONOCYTE ACTIVATION IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS
- 1Instituto de Investigaciones Médicas, Facultad de Medicina, University of Antioquia, Colombia
- 2Sede de Investigación Universitaria, University of Antioquia, Colombia
- 3Sección de Reumatología, Hospital Universitario de San Vicente Fundación, Colombia
Microparticles (MPs) are vesicles derived from the plasma membrane of different cells, are considered a source of circulating autoantigens and can form immune complexes (MPs-ICs). The number of MPs and MPs-ICs increases in patients with systemic lupus erythematosus (SLE). MPs activate myeloid cells by inducing IL-6 and TNF-α in both SLE and other diseases. Therefore, we propose that the recognition of MPs-ICs by monocytes rather that MPs may define their phenotype and contribute to the inflammatory process in patients with SLE. Thus, the aims of this study were to evaluate the association among circulating MPs-ICs from different cell sources, alterations observed in monocyte subsets and disease activity in patients with SLE and to establish whether monocytes bind and respond to MPs-ICs in vitro.
Circulating MPs and monocyte subsets were characterized in 60 patients with SLE and 60 healthy controls (HCs) using multiparametric flow cytometry. Patients had higher MP counts and frequencies of MPs-CD41a+ (platelet-derived) compared with HCs, regardless of disease activity. MPs from patients with SLE were C1q+ and formed ICs with IgM and IgG. MPs-IgG+ were positively correlated with active SLE (aSLE), whereas MPs-IgM+ were negatively correlated. Most of the circulating total ICs-IgG+ were located on MPs. The proportion and number of non-classical monocytes were significantly decreased in patients with SLE compared with HCs and in patients with aSLE compared with patients with the inactive disease. Non-classical monocytes obtained from patients with SLE exhibited increased levels of CD64 associated with MPs-IgG+, MPs-C1q+, total circulating ICs-IgG+ and disease activity.
The direct effects of MPs and MPs-IgG+ on monocytes were evaluated in cell culture. Monocytes from both HCs and patients bound to and internalized MPs and MPs-IgG+ independent of CD64. These vesicles derived from platelets (PMPs), mainly PMPs-IgG+, activated monocytes in vitro and increased the expression of CD69, CD64 and pro-inflammatory cytokines such as IL-1β, TNF-α and IFN-α.
Therefore, MPs are one of the most representative sources of the total amount of circulating ICs-IgG+ in patients with SLE. MPs-IgG+ are associated with SLE activity, and PMPs-IgG+ stimulate monocytes, changing their phenotype and promoting pro-inflammatory responses related to disease activity.
Keywords: microparticles, Monocyte activation, immune complexes, systemic lupus erythematosus, monocyte subsets
Received: 11 Sep 2017;
Accepted: 05 Feb 2018.
Edited by:Philippe Saas, INSERM UMR1098 Interactions Hôte-Greffon-Tumeur & Ingénierie Cellulaire et Génique, France
Reviewed by:Adam B. CEROI, Ghent University, Belgium
Johan Van Der Vlag, Radboud University Nijmegen, Netherlands
Copyright: © 2018 Burbano, Juan Villar-Vesga, Orejuela, Muñoz, Vanegas, Vasquez, Rojas and Castaño. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Mrs. Diana Castaño, University of Antioquia, Instituto de Investigaciones Médicas, Facultad de Medicina, Calle 70 No 52-21, Medellín, 050021, Colombia, email@example.com