Synthesis of alpha 1-antichymotrypsin and alpha 1-antitrypsin by human trophoblast.
alpha 1-Antichymotrypsin (alpha 1-ACHY) and alpha 1-antitrypsin (alpha 1-AT) are closely related glycoprotein protease inhibitors, present in plasma and other extracellular fluids, that neutralize proteases released by leukocytes in response to trauma and inflammatory stimuli. Both inhibitors are synthesized primarily by hepatocytes, although lower levels of synthesis by monocytes and breast and intestinal epithelial cells have been demonstrated. Recently, the immunohistochemical localization of alpha 1-AT and alpha 1-ACHY in intrauterine and extrauterine human trophoblastic tissue has been reported. In the present study, we have sought to determine whether human trophoblast is also able to synthesize alpha 1-AT and alpha 1-ACHY. Messenger RNA for both inhibitors was found by Northern blotting in chorionic villi obtained from first trimester and term placenta. Substantial differences in messenger levels for both inhibitors among individual placentas were noted. alpha 1-ACHY and alpha 1-AT messenger was also present in trophoblast cells in primary culture. Synthesis of alpha 1-AT and alpha 1-ACHY protein was demonstrated by SDS-PAGE after immunoprecipitation of [35S]-labeled alpha 1-AT and alpha 1-ACHY from conditioned media of trophoblast cells in culture metabolically labeled with [35S]-methionine. It is of some interest that the M(r) of the alpha 1-AT and alpha 1-ACHY secreted by trophoblast were 50,000 and 49,000, respectively, compared with 54,000 and 68,000 for these proteins in plasma (or secreted by HepG2 human hepatoma and MCF-7 human breast cancer cells).(ABSTRACT TRUNCATED AT 250 WORDS)
Bergman
D
D
Department of Obstetrics and Gynecology, New York University Medical Center, New York 10016.
Kadner
S S
SS
Cruz
M R
MR
Esterman
A L
AL
Tahery
M M
MM
Young
B K
BK
Finlay
T H
TH
D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D002824:Chorionic Villi / Q000201:enzymology; D005260:Female; D005865:Gestational Age; D006031:Glycosylation; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology; D009363:Neoplasm Proteins / Q000096:biosynthesis; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000096:biosynthesis*; D011499:Protein Processing, Post-Translational; D014327:Trophoblasts / Q000201:enzymology*; D014407:Tumor Cells, Cultured; D000514:alpha 1-Antichymotrypsin / Q000096:biosynthesis*; D000515:alpha 1-Antitrypsin / Q000096:biosynthesis*
D009363:Neoplasm Proteins; D011257:Pregnancy Proteins; D000514:alpha 1-Antichymotrypsin; D000515:alpha 1-Antitrypsin