Ontogeny of membrane cofactor protein: phenotypic divergence in the fetal heart.
Human adult cells are protected from complement-induced damage in part by membrane cofactor protein (MCP, CD46). To examine fetal characteristics which might influence autoantibody-mediated diseases acquired in utero, such as heart block in neonatal lupus, the tissue expression of MCP was studied. Using a high ratio of acrylamide:bisacrylamide, immunoblots of tissues from six fetuses (aged 19-24 weeks) probed with rabbit anti-MCP antibodies revealed a band at 60 KD in addition to the known 65 KD and 55 KD isoforms which comprise the codominant allelic system of MCP. Five fetuses expressed the most common MCP polymorphism (predominance of the 65 KD isoform, upper band alpha-phenotype) in the kidney, spleen, liver and lung. In contrast, all hearts from these five fetuses demonstrated a different pattern in which there was a marked decrease in the intensity of the 65 KD band and accentuation of the lower molecular weight bands. In a sixth fetus, which expressed the second most common polymorphism (equal expression of the 65 KD and 55 KD MCP isoforms, alpha beta-phenotype), the heart was similar to the other tissues. These studies confirm the expression of MCP in early gestational life. Preferential expression of the MCP beta-isoform in the majority of fetal hearts irrespective of the phenotype of other organs, suggests tissue-specific RNA splicing or post-translational modification which may relate to autoantibody-mediated injury in diseases such as neonatal lupus.
Gorelick
A
A
Department of Rheumatology, Hospital for Joint Diseases, New York University School of Medicine, New York 10003, USA.
Oglesby
T
T
Rashbaum
W
W
Atkinson
J
J
Buyon
J P
JP
D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D005333:Fetus / Q000378:metabolism* / Q000473:pathology; D005865:Gestational Age; D006801:Humans; D015151:Immunoblotting; D008180:Lupus Erythematosus, Systemic / Q000378:metabolism* / Q000473:pathology; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D010641:Phenotype; D011110:Polymorphism, Genetic
D015703:Antigens, CD; C497857:CD46 protein, human; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins