Related Experiment Videos
Complement regulatory proteins in early human fetal life: CD59, membrane co-factor protein (MCP) and
K L Simpson1, J M Houlihan, C H Holmes
1University of Bristol, Department of Obstetrics and Gynaecology, St Michael's Hospital, U.K.
Insights
Human fetuses express complement regulatory proteins like CD59 and membrane co-factor protein (MCP) in the liver early in gestation. These proteins, crucial for fetal protection, show distinct expression patterns and developmental regulation, particularly MCP loss in adult hepatocytes.
Area of Science:
- Immunology
- Developmental Biology
- Fetal Medicine
Background:
- The human fetus requires protection from maternal complement (C) early in development.
- Complement regulatory proteins (CRPs) like decay-accelerating factor (DAF), membrane co-factor protein (MCP), and CD59 are expressed on trophoblast at the feto-maternal interface.
- The liver is a significant site of fetal hematopoiesis and a potential site for CRP expression within the fetus.
Purpose of the Study:
- To investigate the ontogeny and distribution of CRPs (DAF, MCP, CD59) within the developing human fetus, focusing on the liver.
- To understand the developmental regulation of these proteins in the fetal liver and compare their expression to adult liver and placental trophoblast.
Main Methods:
- Immunohistochemical staining of fetal liver tissue to detect DAF, MCP, and CD59 expression.
- Immunoblotting of fetal liver extracts to confirm the presence and molecular weight of CRPs.
- Comparison of CRP distribution and expression patterns between fetal and adult liver, and with placental trophoblast.
Main Results:
- DAF, MCP, and CD59 are expressed in the fetal liver from at least 6 weeks of gestation.
- CD59 shows broad distribution in both epithelial and hematopoietic compartments.
- DAF is restricted to isolated hematopoietic cells, while MCP is present on hematopoietic cells and strongly expressed on developing hepatic epithelium.
- MCP exhibits developmental regulation, with a notable loss of expression in adult hepatocytes compared to fetal hepatic epithelium.
- Differences in molecular weight for MCP were observed between fetal liver and placental trophoblast.
Conclusions:
- Complement regulatory proteins, particularly CD59 and MCP, are expressed early in fetal liver development (from 6 weeks gestation).
- MCP is developmentally regulated in the human liver, expressed on early hepatic epithelium in the absence of DAF.
- These findings suggest that CRPs are essential for protecting the developing fetus from complement-mediated damage from early gestation onwards.
Abstract:
The human fetus appears to be capable of protecting itself from maternal complement (C) from an early stage in development by expressing the C regulatory proteins decay-accelerating factor (DAF), membrane co-factor protein (MCP) and CD59 on fetally derived trophoblast at the feto-maternal interface. In this study we have examined the ontogeny of these proteins within the fetus itself and have focused on the liver which represents a major site of haemopoiesis during development. Immunostaining revealed that DAF, MCP and CD59 are all expressed from at least 6 weeks of gestation in the liver but that these proteins display distinct distribution patterns. CD59 was broadly distributed both within the epithelial and haemopoietic compartments, but expression of C3 convertase regulators was more restricted. DAF expression was limited to isolated cells within haemopoietic nests and the epithelium was DAF-negative. Although MCP expression on haemopoietic cells was also limited, by contrast with DAF the developing hepatic epithelium was strongly MCP-positive. Typical CD59 and MCP components were observed in fetal liver extracts by immunoblotting, although liver MCP components consistently migrated 4000-5000 MW ahead of those observed on placental trophoblast. Differences in the distribution of these proteins were also observed between the fetal and adult liver. In particular, by comparison with fetal hepatic epithelium, there was an apparent loss of MCP expression from adult hepatocytes. Thus, MCP appears to be developmentally regulated in the human liver and is expressed in the absence of DAF on the early hepatic epithelium. Overall, this study suggests that C regulatory proteins, and in particular CD59 and MCP, are required from the very early stages of gestation within the fetus itself.