Decay-accelerating factor protects human trophoblast from complement-mediated attack.
Approximately one-fifth of first trimester losses can be characterized by the onset of hypocomplementemia prior to ultrasonographic loss of embryonic viability. Monoclonal antibodies to the membrane complement regulatory protein, decay-accelerating factor (DAF), were bound to the surface of trophoblastic tissues, with the estimated number of DAF molecules in tissues obtained from hypocomplementemic women less than those from normocomplementemic women (approximately 10%). While trophoblastic tissue obtained from normocomplementemic women did not decomplement normal human sera, pretreatment of this tissue with anti-DAF antibodies resulted in activation of the complement (C') system via the alternate C' pathway (ACP). If trophoblastic tissue from normocomplementemic women was pretreated with phospholipase C, decomplementation of human serum occurred. These data strongly suggest that trophoblasts evade the ACP with functional DAF, possibly through absorption of the molecule's lipophilic diacylglycerol membrane-anchored moiety into the outer lipid bilayer of the trophoblast and may be a rational means for the utilization of immunotherapy in recurrent spontaneous aborters.
Cunningham
D S
DS
Department of Obstetrics and Gynecology, National Naval Medical Center, Bethesda, Maryland 20889-5000.
Tichenor
J R
JR
D000026:Abortion, Habitual / Q000276:immunology*; D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000502:physiology*; D018958:CD55 Antigens; D015941:Complement Hemolytic Activity Assay; D003169:Complement Inactivator Proteins / Q000502:physiology*; D003170:Complement Pathway, Alternative; D005260:Female; D006801:Humans; D008562:Membrane Glycoproteins / Q000502:physiology*; D011247:Pregnancy; D014327:Trophoblasts / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018958:CD55 Antigens; D003169:Complement Inactivator Proteins; D008562:Membrane Glycoproteins