SUSCEPTIBILITY OF HUMAN TROPHOBLAST TO KILLING BY HUMAN-COMPLEMENT AND THE ROLE OF THE COMPLEMENT REGULATORY PROTEINS

The susceptibility of trophoblast to cytolysis by human complement was investigated using cells purified to over 90% from first trimester pl acentae. Two assay systems were employed to measure the killing of tro phoblasts, an antibody-dependent complement-mediated cytolysis and the reactive lysis. The antibody obtained from a patient with Addison's d isease reacted specifically with syncytiotrophoblasts and induced a do se-dependent killing of the cells not exceeding 50% even in the presen ce of excess antibody and complement. The percentage of cells killed b y the terminal complement complex in the reactive lysis system was som ewhat higher, reaching values of 60%. Immunofluorescence analysis reve aled the presence of CD46 and CD59 on all syncytiotrophoblasts, wherea s CD55 was only detected on approximately 30% of the cells. Inhibition of CD46 and CD59 resulted in increased susceptibility of syncytiotrop hoblasts to complement lysis. The protective function of CD55 could no t be evaluated because of its reduced expression on isolated trophobla sts. These results suggest that syncytiotrophoblasts may be killed by complement and that membrane regulators to some extent protect these c ells from complement damage.