title: Complement regulatory proteins in early human fetal life: CD59, membrane co-factor protein (MCP) and decay-accelerating factor (DAF) are differentially expressed in the developing liver.
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.
authors.affiliation: University of Bristol, Department of Obstetrics and Gynaecology, St Michael's Hospital, U.K.
authors.forename: K L
authors.initials: KL
authors.lastname: Simpson
authors.forename: J M
authors.initials: JM
authors.lastname: Houlihan
authors.forename: C H
authors.initials: CH
authors.lastname: Holmes
mesh_terms: D000328:Adult; D000375:Aging / Q000276:immunology; D015703:Antigens, CD / Q000032:analysis*; D015153:Blotting, Western; D018958:CD55 Antigens; D018957:CD59 Antigens; D003169:Complement Inactivator Proteins / Q000032:analysis*; D003165:Complement System Proteins / Q000276:immunology; D006801:Humans; D007124:Immunoenzyme Techniques; D008099:Liver / Q000196:embryology* / Q000276:immunology; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins / Q000032:analysis*
chemical_list: D015703:Antigens, CD; C497857:CD46 protein, human; D018958:CD55 Antigens; D018957:CD59 Antigens; D003169:Complement Inactivator Proteins; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins; D003165:Complement System Proteins