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Complement regulatory proteins at the feto-maternal interface during human placental development: distribution of
C H Holmes1, K L Simpson, H Okada
1University of Bristol, Department of Obstetrics and Gynaecology, St. Michael's Hospital, Great Britain.
Insights
Complement regulatory proteins like decay-accelerating factor (DAF) and membrane cofactor protein (MCP) protect the developing human placenta. Their differential expression on trophoblast cells suggests specific roles throughout gestation.
Area of Science:
- Immunology
- Developmental Biology
- Reproductive Science
Background:
- The human placenta requires protection from maternal complement (C) attack.
- Complement regulatory proteins (CRPs) like DAF (CD55), MCP (CD46), and CD59 are crucial for self-non-self discrimination.
- These proteins control C3 convertases and the membrane attack complex (MAC).
Purpose of the Study:
- To investigate the presence and distribution of DAF, MCP, and CD59 in the developing human placenta.
- To understand the role of these CRPs in protecting the fetally derived conceptus from maternal C.
- To explore differential expression patterns of CRPs on various trophoblast populations.
Main Methods:
- Immunohistochemistry was used to visualize DAF, MCP, and CD59 distribution on placental tissues.
- Solid-phase binding assays were performed on isolated trophoblast membranes.
- Transcript abundance for CD59 and DAF was assessed in purified trophoblast cells.
Main Results:
- DAF, MCP, and CD59 are present from early gestation (6 weeks) to term.
- Differential expression of DAF and MCP was observed on villous cytotrophoblast and syncytiotrophoblast.
- CD59 expression was high on syncytiotrophoblast, villous cytotrophoblast, and extra-villous trophoblast.
Conclusions:
- Complement regulatory proteins are vital for protecting the human conceptus throughout pregnancy.
- Distinct expression patterns of DAF, MCP, and CD59 on trophoblast cells suggest specialized functions.
- These differential expressions may indicate varying requirements for C regulation at different placental sites.
Abstract:
The complement (C) regulatory proteins decay-accelerating factor (DAF, CD55) and membrane cofactor protein (MCP, CD46), which control C3 convertases, together with CD59, an inhibitor of the membrane attack complex (MAC), were found to be present in the developing human placenta from at least 6 weeks of gestation until term. Immunostaining revealed differences in the distribution of these proteins on the fetally derived trophoblast epithelium, especially in early placentae which contain trophoblast populations of diverse proliferative potential and differentiation status. Expression of all three proteins occurred on the terminally differentiated syncytiotrophoblast epithelium covering chorionic villi and which is in direct contact with maternal blood. CD59 was also expressed on the underlying villous cytotrophoblast cells and on their extra-villous derivatives. These two populations showed differential expression of the C3 convertase regulators. Villous cytotrophoblast cells expressed MCP but were largely devoid of DAF. Proliferation of this population to generate extra-villous cytotrophoblast cell columns was associated with both an increase in DAF expression and a decrease in MCP expression. Throughout placental development, expression of DAF appeared to be lower than that of MCP and CD59 as assessed by solid-phase binding assays on isolated trophoblast membranes. Early placentae were also found to contain both DAF+ and DAF- chorionic villi. Conversely, expression of CD59 appeared comparatively high and transcripts for CD59 were found to be much more abundant than those for DAF in purified trophoblast cells. C regulatory proteins appear to play an important role throughout gestation in protecting the fetally derived human conceptus from maternal C. The differential expression patterns of the proteins on trophoblast may reflect differences in requirement for specific functional activities at different locations within the placenta.