COMPLEMENT REGULATORY PROTEINS IN EARLY HUMAN FETAL LIFE - CD59, MEMBRANE COFACTOR PROTEIN (MCP) AND DECAY-ACCELERATING FACTOR (DAF) ARE DIFFERENTIALLY EXPRESSED IN THE DEVELOPING LIVER

The human fetus appears to be capable of protecting itself from matern al complement (C) from an early stage in development by expressing the C regulatory proteins decay-accelerating factor (DAF), membrane co-fa ctor protein (MCP) and CD59 on fetally derived trophoblast at the feto -maternal interface. In this study we have examined the ontogeny of th ese proteins within the fetus itself and have focused on the liver whi ch represents a major site of haemopoiesis during development. Immunos taining revealed that DAF, MCP and CD59 are all expressed from at leas t 6 weeks of gestation in the liver but that these proteins display di stinct distribution patterns. CD59 was broadly distributed both within the epithelial and haemopoietic compartments, but expression of C3 co nvertase regulators was more restricted. DAF expression was limited to isolated cells within haemopoietic nests and the epithelium was DAF-n egative. Although MCP expression on haemopoietic cells was also limite d, 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 consis tently migrated 4000-5000 MW ahead of those observed on placental trop hoblast. Differences in the distribution of these proteins were also o bserved between the fetal and adult liver. In particular, by compariso n with fetal hepatic epithelium, there was an apparent loss of MCP exp ression from adult hepatocytes. Thus, MCP appears to be developmentall y regulated in the human liver and is expressed in the absence of DAF on the early hepatic epithelium. Overall, this study suggests that C r egulatory proteins, and in particular CD59 and MCP, are required from the very early stages of gestation within the fetus itself.