Murine embryonic survival depends on regulation of complement: Xu, C. et al. (2000) A critical role for murine complement regulator Crry in fetomaternal tolerance. Science 287, 498–501

Abstract

Activation of the complement system is a feature of both the innate and adaptive arms of the immune response. As a component of natural immunity, complement activation leads to enhanced phagocytosis, clearance of immune complexes, chemotaxis of inflammatory cells and cell lysis. Although complement can bind to self tissues, cells are protected because they express proteins that inactivate complement. In humans, decay accelerating factor (DAF) and membrane cofactor protein (MCP) are involved in inactivation of complement components. In rodents, a third protein, Crry, is also involved in complement regulation.In this study, Xu and colleagues set out to generate Crry-knockout mice to investigate in vivo the role of Crry in protecting against complement attack. However, no live Crry−/− mice were recovered, indicating that Crry plays a crucial role in pregnancy. Crry−/− embryos died at day 10 after conception. Complement deposition was detected in both the embryo and placenta, as well as infiltration of inflammatory cells. Crossing the Crry+/− mice with C3−/− mice (in which complement is inactive) produced 27% of pups that were Crry−/−, indicating that complement activation was the cause of the embryonic lethality of the Crry−/− mice.Although mice possess DAF and MCP as well as Crry, neither DAF nor MCP are expressed in early embryos, leaving Crry as the crucial regulator of complement activation at this stage of murine development. Crry does not exist in humans, but DAF and MCP are both expressed in human placentas. Xu and colleagues propose that DAF and MCP play a similar role to Crry in controlling complement-mediated inflammation and tissue damage in early human pregnancy.