Atorvastatin down-regulates the primate cellular response to porcine aortic endothelial cells in vitro.
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.
Ezzelarab
Mohamed
M
Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, PA 15261, USA. ezzelarabmb@upmc.edu
Welchons
Daniel
D
Torres
Corine
C
Hara
Hidetaka
H
Long
Cassandra
C
Yeh
Peter
P
Ayares
David
D
Cooper
David K
DK
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
D006538:Heptanoic Acids; D011758:Pyrroles; D000069059:Atorvastatin
J Immunol. 2003 Feb 1;170(3):1524-30
12538717
Nat Med. 2000 Dec;6(12):1399-402
11100127
Transplantation. 2006 Mar 27;81(6):922-6
16570018
J Immunol. 2007 Sep 15;179(6):3613-21
17785796
Int Immunol. 2007 Feb;19(2):163-73
17182966
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 1998 Nov;12(6):359-62
10437092
Am J Transplant. 2004 Jul;4(7):1013-8
15196056
J Exp Med. 2003 Mar 17;197(6):725-33
12629065
Nat Med. 2001 Jun;7(6):687-92
11385505
Xenotransplantation. 2007 Mar;14(2):100-3
17381683
Cell Transplant. 2003;12(6):637-46
14579932
Nature. 2002 Nov 7;420(6911):78-84
12422218
Transplantation. 2000 Mar 15;69(5):940-4
10755554
J Immunol. 1995 Dec 1;155(11):5249-56
7594537