A transforming growth factor beta 2 (TGF-beta 2)-like immunosuppressive factor in amniotic fluid and localization of TGF-beta 2 mRNA in the pregnant uterus.
This report describes a murine amniotic fluid (MAF) immunosuppressive factor that has properties similar to transforming growth factor beta (TGF-beta). The MAF factor exhibits TGF-beta-like activity in stimulating soft agar colony formation by AKR-2B cells and inhibiting thymidine uptake by Mv1Lu cells. We demonstrate that both the immunosuppressive and TGF-beta-like activities of the MAF factor are completely neutralized by anti-TGF-beta 2-specific antibodies and not by anti-TGF-beta 1-specific antisera. The immunosuppressive factor in MAF is novel in that it appears to be identical or very closely related to TGF-beta 2 and is active in its native state. This active and anti-TGF-beta 2-neutralizable factor chromatographs at approximately 70 kD on Sephadex at neutral pH and appears to be able to complex with alpha-fetoprotein in native amniotic fluid. Chromatography of native MAF under acidic conditions demonstrates a lower molecular mass protein that chromatographs on BioGel in the same position as the mature 25-kD TGF-beta. This protein has the biological properties of TGF-beta and is immunosuppressive. Both of these activities are neutralizable with anti-TGF-beta 2 but not with anti-TGF-beta 1 or other antisera. By Northern analysis, we find high levels of TGF-beta 2 mRNA (with little or no TGF-beta 1) in the pregnant uterus that peak around day 15 of gestation and then fall rapidly by day 19 as birth approaches. The TGF-beta 2-like factor could possibly play a role in maternal immunity, in the retention of the fetal allograft, as well as in regulating fetal and neonatal immunological competence.
Altman
D J
DJ
Department of Molecular Medicine and Immunology, Roswell Park Cancer Institute, Buffalo, New York 14263.
Schneider
S L
SL
Thompson
D A
DA
Cheng
H L
HL
Tomasi
T B
TB
D000653:Amniotic Fluid / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn / Q000276:immunology / Q000378:metabolism; D015152:Blotting, Northern; D002850:Chromatography, Gel / Q000379:methods; D003115:Colony-Stimulating Factors / Q000032:analysis; D005260:Female; D005333:Fetus / Q000276:immunology / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000032:analysis*; D051379:Mice; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000032:analysis* / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D014599:Uterus / Q000737:chemistry* / Q000378:metabolism; D000509:alpha-Fetoproteins / Q000378:metabolism
D003115:Colony-Stimulating Factors; D007166:Immunosuppressive Agents; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D000509:alpha-Fetoproteins