Op0157 Ccl2-Ccr2 Axis Mediates Decidual Monocyte/Macrophage Infiltration and Inflammation in Obstetric Antiphospholipid Syndrome

Background: Obstetric antiphospholipid syndrome (OAPS) is an autoimmune disorder associated with pathologic pregnancy. Decidual inflammation was found to be a critical pathogenesis of OAPS, but the characteristic and regulator was unrevealed. We found significant monocyte/macrophage infiltration in decidua of OAPS patients before, as well as the overexpression of CCL2, which were related to decidual inflammation. However, the detail effect of CCL2-CCR2 axis in OAPS was unclear. Objectives: To investigate the effect and mechanism of CCL2-CCR2 axis in decidual monocyte/macrophage infiltration and inflammation among OAPS. Methods: The first-trimester decidua and peripheral blood samples from OAPS patients and healthy controls who matched for age and gestational weeks were collected, and pregnant mice were injected with mouse-anti human ß2 glycoprotein I (ß2GPI) monoclonal antibody to induce OAPS. The expressions of CCL2 and CCR2 in decidua and peripheral blood were detected by immunohistochemistry, enzyme-linked immunosorbent assay and flow cytometry. Transwell was used to detect the chemotaxis of primary decidual cells to THP-1 cell line. The monocyte/macrophage infiltration and inflammation of blocking CCL2-CCR2 signaling in OAPS mice was investigated by bindarit, a CCL2 inhibitor, and RS504393, a CCR2 antagonist. The main source and distribution of decidual CCL2 were explored by immunofluorescence staining. Results: The CCL2 levels in decidua and serum, and the expressions of CCR2 on decidual macrophages and peripheral monocytes, were significantly higher in both OAPS patients and mice than controls. A higher proportion of decidual macrophage and lower proportion of monocytes were observed in both OAPS patients and mice compared to controls. Also, we validated the positive correlations between decidual CCL2 levels, CCR2 levels in decidual macrophage and the proportion of decidual macrophage. The primary decidual cells from OAPS patients recruited more THP-1 cells than those from controls in vitro, and after bindarit stimulating and RS504393 blocking, this chemotactic effect was inhibited. OAPS mice that received bindarit and RS504393 treatment also presented less decidual monocyte/macrophage infiltration, less inflammatory cytokines, such as TNF-α, IFN-γ and IL-1ß, in decidua, and lower embryo absorption rate. Decidual macrophages and vascular endothelial cells were the main source of CCL2, and CCL2 was mainly distributed in the decidual interstitium and surface of vascular vessels in OAPS. Conclusion: The CCL2-CCR2 axis mediates monocyte/macrophage infiltration from peripheral blood to decidua, and subsequent inflammation, among OAPS. We provide a new insight into the mechanism and therapeutic target for OAPS. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests: None declared.