Early embryonic cells activate the alternative complement system

Murine embryonic stem cells, embryonic carcinoma cells and pre-implantation embryos were found to be extremely sensitive to cytolysis by normal human serum as compared to matured cells. The cytolytic activity to embryonic cells was not removed by pre-absorption of serum with spleen lymphocytes. Conditions which block both complement activation pathways or, selectively, the alternative pathway completely abrogated the activity of human serum against embryonic cells whereas the activity was retained under conditions which block the classical complement pathway, indicating that embryonic cells activate the alternative complement system (ACS). The cytotoxic effect to murine embryonic cells was reproduced using syngeneic murine serum. Concerning the mechanism of ACS-activation, the expression of regulators of complement activation and of membrane bound sialic acid was analysed. Embryonic cells express mRNA for Crry similarly to other cells but additionally express Cr2-transcripts not found in most adult cells. Embryonic cells have strikingly low levels of membrane-bound sialic acid compared to adult cells.