Mitigating placental injuries through up-regulating DAF in experimental APS mice: new mechanism of progesterone. (20th June 2019)

• Record Type: Journal Article
• Authors: Zhang, Y; Jin, S
• Is Part Of: Clinical and experimental immunology. Volume 197:Number 3(2019)
• Page Start: 376
• Page End: 386
• Publication Date: 2019-06-20
• Subjects: anti-phospholipid syndrome -- complement -- decay accelerating factor -- progesterone; Immunopathology -- Periodicals; 616.079
• DOI: 10.1111/cei.13313
• Languages: English
• ISSNs: 0009-9104

Abstract

Summary: Anti-phospholipid syndrome (APS) is characterized by recurrent pathological pregnancy, arterial or venous thrombosis in the presence of anti-phospholipid antibody (aPL). Complement activation is recognized as an intermediate link leading to placental thrombosis and placental inflammation in APS model mice. Decay accelerating factor (DAF, CD55), MAC-inhibitory protein (MAC-IP, CD59) and membrane co-factor protein (MCP, CD46) are important complement inhibitory proteins (CIPs) highly expressed in normal placenta to curb excessive complement activation and its mediated injuries. Anti-β2 glycoprotein I (anti-β2GPI) antibody is an important aPL. We found that placental DAF and CD46 decreased in β2GPI passively immunized APS model mice, accompanied by C3 deposition, neutrophil infiltration and increased proinflammatory cytokine levels detected in its placenta. Progesterone supplement can up-regulate DAF but not CD46 expression, curb C3 activation and decrease proinflammatory cytokines levels to reduce fetal loss frequency. Progesterone receptor antagonist (mifepristone) or knock-down DAF with specific siRNA, above the protective effects of progesterone, were significantly weakened. Another sex hormone, oestrogen, has no significant effect on placental DAF and C3 contents and fetal loss frequency in the APS mice model. This may be an important mechanism by which progesterone induces maternal–fetal immune tolerance. At the same time, it may provide evidence for the use of progesterone in APS abortion patients. Graphical Abstract: