title: Estradiol inhibits allograft-inducible major histocompatibility complex class II antigen expression and transplant arteriosclerosis in the absence of immunosuppression.
abstract: BACKGROUND
  The etiology of transplant arteriosclerosis is unknown, but current data point to the alloimmune response. Previously, we found that estradiol-17beta (E2) with immunosuppressant cyclosporine abolishes major histocompatibility complex (MHC) class II expression in the allograft. This study determines the effect of E2 on MHC class II antigen expression in the allograft, in the absence of immunosuppression.
  
  
  METHODS
  Lewis male rats received orthotopic abdominal aorta allografts from male Brown-Norway rats. The recipients were treated continuously subcutaneously with either 20 microg x kg(-1) x day1 of E2 (n=20) or placebo (n=20), from 2 days before transplantation until death on posttransplant days 1, 3, 7, and 14. The allografts were harvested and processed for morphometry and for immunohistochemical staining of MHC class II antigens, macrophages, CD4 and CD8 T lymphocytes, interferon-gamma (IFN-gamma), and IFN-gamma receptor.
  
  
  RESULTS
  With E2 treatment, we observed that inducible MHC class II antigen expression is abolished in the media of the vascular allograft; the expression of IFN-gamma and IFN-gamma receptor is unaffected; and macrophage infiltration of the vascular allograft is inhibited significantly (P<0.01), whereas the CD4 and CD8 T lymphocytes are not significantly (P=0.07) suppressed. The myointimal hyperplasia in the allografts from E2-treated-recipients was 3-4-fold less than that from the placebo-treated recipients.
  
  
  CONCLUSIONS
  Without immunosuppression, E2 inhibition of transplant arteriosclerosis is still associated with inhibition of inducible MHC class II antigen expression in the allografts. The estradiol-17beta abolition of inducible MHC class II antigen expression in the aorta allograft occurs in spite of up-regulation of IFN-gamma ligand and receptor protein.
authors.affiliation: Department of Surgery, Georgetown University Medical Center, Washington, DC 20007, USA.
authors.forename: S
authors.initials: S
authors.lastname: Saito
authors.forename: M L
authors.initials: ML
authors.lastname: Foegh
authors.forename: N
authors.initials: N
authors.lastname: Motomura
authors.forename: H
authors.initials: H
authors.lastname: Lou
authors.forename: K
authors.initials: K
authors.lastname: Kent
authors.forename: P W
authors.initials: PW
authors.lastname: Ramwell
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D001012:Aorta, Abdominal / Q000637:transplantation; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000473:pathology; D004958:Estradiol / Q000097:blood / Q000494:pharmacology*; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis* / Q000187:drug effects; D007371:Interferon-gamma / Q000096:biosynthesis; D008264:Macrophages / Q000166:cytology; D008297:Male; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D017471:Receptors, Interferon / Q000096:biosynthesis; D014184:Transplantation, Homologous / Q000276:immunology / Q000473:pathology / Q000502:physiology; D000096743:Interferon gamma Receptor
chemical_list: D004958:Estradiol; D000949:Histocompatibility Antigens Class II; D007371:Interferon-gamma; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor