Mitigating placental injuries through up-regulating DAF in experimental APS mice: new mechanism of progesterone

Author:

Zhang Y1,Jin S12ORCID

Affiliation:

1. Department of Traditional Chinese Medicine, Maternal and Child Health Hospital of Hubei Province, Hubei, China

2. First Clinical Medical College, Hubei University of Chinese Medicine, Hubei, China

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.

Funder

Hubei Provincial Health and Family Planning Commission Joint Innovation Team Project

the Key Project of Hubei Provincial Health and Family Planning Commission Fund

Publisher

Oxford University Press (OUP)

Subject

Immunology,Immunology and Allergy

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