Complement and pregnancy: new insights into the immunobiology of the fetomaternal relationship.
Recent studies have revealed that human trophoblast expresses three membrane-bound proteins which function specifically to regulate the activity of complement. These proteins are already known to be widely distributed in normal adult tissues where they protect host cells from damage resulting from the fortuitous deposition of activated complement components. Their activities are focused at two distinct steps in the complement pathway. Decay accelerating factor (DAF, CD55) and membrane co-factor protein (MCP, CD46) act at the level of the C3 convertase enzymes which activate C3 to C3b. A further protein, CD59, directly regulates the formation and function of the terminal cytolytic membrane attack complex (MAC) by specifically interacting with C8 and C9. These proteins appear to play an important role in the maintenance of normal human pregnancy. DAF, MCP and CD59 are all expressed where trophoblast surfaces are in contact with maternal blood and tissues and expression occurs from at least 6 weeks of gestation. The semi-allogeneic human conceptus therefore appears to be effectively protected from maternal complement-mediated damage arising either from alternative or classical pathway activation or in a bystander fashion following a response to microbial infection in the mother. Complement regulatory protein deficiency disorders with clinically demonstrable consequences especially in terms of haemolytic disease are known to exist and have proved valuable in establishing the biological role of these proteins in vivo. The demonstration of this new family of immunoregulatory proteins on trophoblast raises important questions about the potential involvement of these products in pregnancy pathologies.
Holmes
C H
CH
University of Bristol, Department of Obstetrics and Gynaecology, St Michael's Hospital, UK.
Simpson
K L
KL
D003176:Complement C3 / Q000276:immunology; D050577:Complement C3-C5 Convertases / Q000276:immunology; D015938:Complement Membrane Attack Complex / Q000276:immunology; D003170:Complement Pathway, Alternative; D003171:Complement Pathway, Classical; D003165:Complement System Proteins / Q000276:immunology*; D005260:Female; D005333:Fetus / Q000276:immunology*; D006801:Humans; D011247:Pregnancy / Q000276:immunology*; D011248:Pregnancy Complications / Q000276:immunology; D014327:Trophoblasts / Q000276:immunology
D003176:Complement C3; D015938:Complement Membrane Attack Complex; D003165:Complement System Proteins; D050577:Complement C3-C5 Convertases