Background/Purpose: Mononuclear phagocytes depurate apoptotic cells, microparticles (MPs), and immune complexes (IC), leading to a tolerant or inflammatory microenvironment. The MPs, vesicular structures mainly produced during activation and cell death, have a wide spectrum of biological activities in intercellular communication. We propose circulating MPs must be recognized by monocytes affecting their frequency, maturation, migration, and function. This could have an impact on the clinic and activity of this disease. Then, monocytes and MPs were studied in the peripheral blood from SLE patients and healthy controls.

Methods: Venous blood samples from patients with SLE and healthy controls were collected. Monocytes subsets (classical, intermediate and non classical) were defined based on the expression of CD14 and CD16 in HLA-DR+ cells, and several phenotypic markers were assessed by multiparametric flow cytometry. MPs were isolated from platelet-poor plasma by ultra-centrifugation and characterized by multiparametric flow cytometry.

Results: SLE patients had elevated percentages of MPs that forming IC, IgM+, and IgM+IgG+, and, MP HMGB1+ and C1q+. We did not observed differences in the number of MPs, size, or in the content of DNA, RNA and phosphatidylserine externalization compared to healthy controls. To understand the possible pathways by which mononuclear phagocytes interact with MPs, we evaluated putative receptors in monocytes. Monocyte subsets from SLE patients have decreased expression of the scavenger receptor CD36. Non-classical monocytes had increased expression of FcgR CD64, but not in CD16, CD32, and TOSO (FcmR). The protein subunit that forms the complement receptor 3 (CR3), CD11b, was reduced in classical and intermediate monocytes. These data suggest that circulating MPs of SLE patients are probably less recognized by monocytes through CD36 and CR3, allowing the recognition of them through FcgR and FcmR.

Classical and intermediate monocytes of these patients had reduced expression of CCR2 and CX3CR1; and the CCR5 was reduced in classical monocytes. This suggests that mainly circulating classical and intermediate monocytes from SLE patients have reduced ability to interact with the endothelium and to migrate in response to fractalkine, monocyte chemoattractant protein 1, RANTES, and macrophage inflammatory protein 1α and 1β. On the other hand, we observed a reduced percentage of circulating non-classical monocytes in SLE patients. This result, together with their normal expression of CX3CR1, suggests that this monocyte subset may be recruited into inflamed tissue as the kidney, where they have been observed augmented.

Conclusion: All these evidences, suggest that circulating MPs may interact with phagocytes from patients in a different way than with healthy controls; mediating alterations on their activation patterns, migration, contact with the endothelium, and induction of tissue damage in SLE patients. The identification of the modulatory effect of these MPs in monocytes will provide new potential targets to develop alternative treatments.

« Back to 2015 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/phenotypically-divergences-of-monocyte-subsets-and-microparticles-in-systemic-lupus-erythematosus-patients/