title: Atorvastatin down-regulates the primate cellular response to porcine aortic endothelial cells in vitro.
abstract: Using mixed lymphocyte reaction (MLR), the effect of atorvastatin on proliferation of human and baboon peripheral blood mononuclear cells (PBMCs) and human CD4+ T cells in response to wild-type (WT) and alpha-1,3-galactosyltransferase gene-knockout (GTKO) porcine aortic endothelial cells (pAECs) was investigated. swine leukocyte antigen class-II (SLA II) expression on pAEC before and after porcine interferon gamma (pIFN-gamma) stimulation, and the effect of atorvastatin on this expression was assessed. Added to the MLR, atorvastatin reduced (i) the human PBMC response to unstimulated (P<0.05) and (ii) the human and baboon PBMC responses to stimulated (P<0.05) WT and GTKO pAEC. Atorvastatin treatment of human PBMC before MLR reduced their response to stimulated WT (P<0.05) and GTKO (P<0.05) pAEC. Stimulation of pAEC with pIFN-gamma increased SLA II expression 20- to 60-fold, which was down-regulated by atorvastatin. Atorvastatin treatment of stimulated pAEC before MLR reduced proliferation of human PBMC (P<0.05) and CD4+ T cells (P<0.05). Atorvastatin down-regulates the primate cellular xenoresponse, possibly through its antiproliferative effect on PBMCs and the reduction of SLA II on pAECs.
authors.affiliation: Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, PA 15261, USA. ezzelarabmb@upmc.edu
authors.forename: Mohamed
authors.initials: M
authors.lastname: Ezzelarab
authors.forename: Daniel
authors.initials: D
authors.lastname: Welchons
authors.forename: Corine
authors.initials: C
authors.lastname: Torres
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Hara
authors.forename: Cassandra
authors.initials: C
authors.lastname: Long
authors.forename: Peter
authors.initials: P
authors.lastname: Yeh
authors.forename: David
authors.initials: D
authors.lastname: Ayares
authors.forename: David K
authors.initials: DK
authors.lastname: Cooper
mesh_terms: D000818:Animals; D001011:Aorta; D000069059:Atorvastatin; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects; D005434:Flow Cytometry; D006538:Heptanoic Acids / Q000494:pharmacology*; D006801:Humans; D011758:Pyrroles / Q000494:pharmacology*; D013552:Swine
chemical_list: D006538:Heptanoic Acids; D011758:Pyrroles; D000069059:Atorvastatin
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