Abstract:
BACKGROUND:T lymphocyte activation mediated by CD28 costimulation plays a critical role in graft rejection. Plant alkaloid tetrandrine, purified from a Chinese antirheumatic herb, is a potent immunosuppressant. Here, we examined its effects on several CD28-costimulated T-cell activities. In addition, such effects were readily compared with the effects of three tetrandrine analogs. METHODS:T lymphocytes were purified from whole blood by negative selection. The stimuli that mimic CD28 costimulation included both anti-CD3 + anti-CD28 monoclonal antibody and PMA+anti-CD28 monoclonal antibody. The determination of CD28-costimulated cell proliferation was performed by tritium uptake, cytokine production by ELISA, cell surface interleukin 2Ra and CD69 expression by flow cytometry, and mixed leukocyte reaction by tritium uptake. Drug cytotoxicity was determined by trypan blue exclusion, propidium iodide staining, and MTT colorimetric assays. RESULTS:Tetrandrine inhibited CD28-costimulated T-cell proliferation and cytokine production through a mechanism different from that of cyclosporine. In addition, tetrandrine down-regulated both T helper 1 and T helper 2 cytokine production in CD4+ and CD8+ T-cell subpopulations. By examining cytokine production and T-cell activation marker expression, we further demonstrated that, among tetrandrine and its analogs tested, dauricine was the most potent suppressor of CD28-costimulated T-cell activities. Furthermore, the different immunosuppressive activities of these compounds were not associated with their cytotoxic capacities. Finally, the unparalleled inhibitory potency of dauricine on both mixed leukocyte reaction and CD28-costimulated T-cell proliferation suggests that dauricine preferentially targeted CD28-costimulated T-cell activities. CONCLUSIONS:This is the first report to show that tetrandrine and its analogs potently inhibited both PMA+CD28-costimulated and CD3 + CD28-costimulated activation of human peripheral blood T cells. Based upon their structural similarity and different immunosuppressive potency, these in vitro data also provide very useful information for further identification and development of more potent and less toxic immunosuppressants to achieve transplantation success.
journal_name
Transplantationjournal_title
Transplantationauthors
Lai JH,Ho LJ,Kwan CY,Chang DM,Lee TCdoi
10.1097/00007890-199911150-00027subject
Has Abstractpub_date
1999-11-15 00:00:00pages
1383-92issue
9eissn
0041-1337issn
1534-6080journal_volume
68pub_type
杂志文章相关文献
TRANSPLANTATION文献大全abstract::Extrinsic denervation and lymphatic disruption impair nutrient absorption after small bowel transplantation. The present study was undertaken to determine whether adding the ileocecal valve with or without the ascending colon would improve the function of a segmental intestinal graft. Five groups of Lewis rats (n = 10...
journal_title:Transplantation
pub_type: 杂志文章
doi:
更新日期:1994-04-15 00:00:00
abstract::Dendritic cell (DC) progenitors were propagated in liquid culture from nonparenchymal cells resident in normal mouse (B10.BR; H-2k, I-E+) liver in response to granulocyte-macrophage colony stimulating factor (GM-CSF). The liver-derived DC progenitors were MHC class II-/dim and did not express counter receptors for CTL...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-199502270-00019
更新日期:1995-02-27 00:00:00
abstract::To determine the degree of graft versus host disease (GVHD) prophylaxis that might be necessary if cord blood (CB) transplantation is more widely applied, we compared human cord blood mononuclear cell (CBMC) and adult peripheral blood mononuclear cell (PBMC) proliferative responses and stimulatory capabilities; to exa...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-199408270-00018
更新日期:1994-08-27 00:00:00
abstract:BACKGROUND:Although clinical data suggest its existence, little is known about the effect of rapamycin derivatives on wound repair. This study aims to delineate the influence of the mammalian target of rapamycin inhibitor everolimus on wound healing in the rat intestine. METHODS:Four groups of 26 male Wistar rats rece...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/01.tp.0000246078.09845.9c
更新日期:2006-12-15 00:00:00
abstract:BACKGROUND:The purpose of this study is to examine the effects of the coronavirus disease 2019 (COVID-19) pandemic on adult lung transplants and report practice changes in the United States. METHODS:A retrospective analysis of a public dataset from the United Network for Organ Sharing was performed regarding adult lun...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/TP.0000000000003522
更新日期:2021-01-01 00:00:00
abstract:BACKGROUND:Liver transplantation is a widely accepted treatment for end-stage liver disease. The aim of our study was to investigate the imbalance between T helper type 17 (Th17) and CD4(+) CD25(+) Foxp3(+) regulatory T (Treg) cells during hepatic allograft rejection in a rodent grafts model because their roles in live...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/TP.0000000000000666
更新日期:2015-06-01 00:00:00
abstract:BACKGROUND:Preemptive kidney transplantation (prior to the institution of dialysis) avoids the morbidity and mortality of dialysis; however, detailed studies of high-risk patients are lacking. The aim of the current study was to compare recent outcomes of preemptive (P) versus nonpreemptive (NP) living donor kidney tra...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/01.tp.0000250555.46539.65
更新日期:2007-01-27 00:00:00
abstract:BACKGROUND:Immunosuppression involves the nature of the immunosuppressive agents and individual differences in patient factors. We investigated whether the effect of mycophenolate mofetil (MMF) is measurable using an in vitro measure of immunocompetence and related its effects to cyclosporine (CsA) in vitro. METHODS:L...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-200108150-00011
更新日期:2001-08-15 00:00:00
abstract:BACKGROUND:Remote ischemic preconditioning (RIPC) protects against liver ischemia reperfusion (IR) injury. An essential circulating mediator of this protection is nitric oxide (NO) induced by lower limb RIPC. One of the mechanisms through which NO generally acts is the soluble guanylyl cyclase-cyclic GMP (sGC-cGMP) pat...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/TP.0b013e31824cd59d
更新日期:2012-05-15 00:00:00
abstract::ICAM-1 is an inducible glycoprotein important in the adhesion, activation, and transmigration of circulating leukocytes across the vascular endothelial monolayer, and it likely plays a key role in the allogeneic response. To determine the reproducibility and significance of variations in resting levels of cell surface...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-199410270-00015
更新日期:1994-10-27 00:00:00
abstract::The overall incidence of malignancy in renal transplant recipients is 100-fold higher compared with age matched controls. Routine clinical evaluation therefore often includes the determination of serum tumor markers AFP, CA19-9, CEA, CA125, CA15-3, PSA, and calcitonin. We evaluated the specificity and the sensitivity ...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-199611270-00021
更新日期:1996-11-27 00:00:00
abstract:BACKGROUND:Perioperative renal dysfunction in liver transplant recipients complicates maintenance immunosuppressive therapy, particularly in patients with hepatitis C. Calcineurin inhibitors exacerbate renal dysfunction and mammalian target-of-rapamycin inhibitors are generally avoided because of perceived perioperativ...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/01.TP.0000438635.44461.2e
更新日期:2014-01-27 00:00:00
abstract::Flow cytometry (FC) T and B cell crossmatches were done retrospectively for 38 cadaver renal transplant recipients (29 first and 9 retransplants--minimum follow-up 12 months) using both current pretransplant serum and peak-reactive sera. An increase in median fluorescence intensity (channel shift) and/or an increase i...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-198803000-00012
更新日期:1988-03-01 00:00:00
abstract::Imaging methods such as nuclear medicine (including positron emission tomography), magnetic resonance imaging, ultrasound, and optical imaging can be used to provide information about the expression of genes, and the location of molecules and cells in intact animals or patients. In the setting of transplantation, this...
journal_title:Transplantation
pub_type: 杂志文章,评审
doi:10.1097/01.tp.0000235530.80305.d2
更新日期:2006-11-15 00:00:00
abstract::The survival of semiallogeneic or fully allogeneic rat kidney allografts was prolonged in some strain combinations with immune complexes formed with hapten-conjugated alloantigens (TNP-Ag) of donor origin and a mouse monoclonal antihapten antibody (anti-TNP). Complexes were administered i.v. at the time of operation--...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-198311000-00001
更新日期:1983-11-01 00:00:00
abstract:BACKGROUND:Increasing use of kidney grafts for simultaneous liver and kidney (SLK) transplants is causing concern about the most effective utilization of scarce kidney graft resources. This study evaluated the impact of implementing the proposed United Network for Organ Sharing SLK transplant policy on outcomes for end...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/TP.0000000000000270
更新日期:2015-02-01 00:00:00
abstract:BACKGROUND:Mixed allogeneic bone marrow chimerism induces tolerance to solid organ grafts. Although we previously reported that partially ablative conditioning with 700 cGy of total body irradiation (TBI) is sufficient to allow for bone marrow engraftment in mice, we determined that a minimum of 1000 cGy was required i...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-199908150-00008
更新日期:1999-08-15 00:00:00
abstract::Previously, we demonstrated that the dose-normalized tacrolimus blood concentration after renal transplantation was associated with a single nucleotide polymorphism (SNP) in the CYP3AP1 gene, probably through linkage with an SNP in the CYP3A5 gene. Individuals with at least one CYP3A5*1 allele synthesize CYP3A5 and CY...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/01.tp.0000151766.73249.12
更新日期:2005-02-27 00:00:00
abstract:BACKGROUND:The aim of this single-center study was to investigate whether trough level adjusted mycophenolate mofetil (MMF) is more efficacious in combination with tacrolimus (TAC) or cyclosporine (CsA) and to evaluate the impact of either drug on MMF dosage. METHODS:Sixty patients (TAC, n = 30; CsA, n = 30) undergoin...
journal_title:Transplantation
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/01.tp.0000129814.52456.25
更新日期:2004-08-27 00:00:00
abstract::Despite previous attempts there is currently no suitable animal model available for xenogeneic graft versus host disease (XGVHD) mediated via human immunocompetent cells. Recently, we have developed an efficient protocol to engraft SCID mice with human peripheral blood lymphocytes (Hu-PBLs). The engraftment efficiency...
journal_title:Transplantation
pub_type: 杂志文章
doi:
更新日期:1995-07-27 00:00:00
abstract:BACKGROUND:The influence of the graft composition on the clinical outcome after allogeneic peripheral blood stem cell (PBSC) transplantation is not well established. METHODS:The cellular composition of the apheretic products obtained from 63 human leukocyte antigen-identical siblings was prospectively correlated with ...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/TP.0b013e3181622e36
更新日期:2008-02-15 00:00:00
abstract::Currently it is not feasible to isolate sufficient numbers of islets from a single pancreas for clinical transplantation. We examined whether small numbers of islets obtained from multiple donors could be used for transplantation. Islets were isolated from four inbred strains of mice (DBA/2, DBA/1, C3H, and A.SW) by a...
journal_title:Transplantation
pub_type: 杂志文章
doi:
更新日期:1988-06-01 00:00:00
abstract::Teratoma 402 AX is an embryo-like tumor cell line originally derived from the testicles of strain 129/J mice. This teratocarcinoma grows well in males and pregnant females but poorly in virgin females when given in small doses. Induction of growth of this tumor is syngeneic and allogeneic virgin females was achieved b...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-197510000-00005
更新日期:1975-10-01 00:00:00
abstract::Mice given a pretransplant i.v. infusion of spleen cells from donors incompatible with the recipients with respect to individual minor H antigens exhibit a delayed rejection of skin grafts from these incompatible donors. Attempts were made to detect suppressor T cells, possibly induced by the i.v. infusion of donor ce...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-199001000-00034
更新日期:1990-01-01 00:00:00
abstract::Natural anti-carbohydrate antibodies are central to hyperacute rejection in ABO-incompatible allotransplantation and in discordant xenotransplantation. ABO-incompatible rejection has been inhibited successfully using intravenous soluble carbohydrates as antibody inhibitors. The approach has been less successful previo...
journal_title:Transplantation
pub_type: 杂志文章
doi:
更新日期:1995-12-15 00:00:00
abstract:BACKGROUND:Historically, ex vivo physiological evaluation of cadaveric renal allografts has been limited to assessing perfusate flow (PF) during hypothermic perfusion preservation (HPP). Using a small animal model, we have previously described a method for continuous monitoring of glomerular filtration rate (GFR) durin...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-199911270-00006
更新日期:1999-11-27 00:00:00
abstract:BACKGROUND:Cold ischemia-reperfusion injury is unavoidable during organ transplantation, and prolonged preservation is associated with poorer function recovery. Cardiotrophin-1 (CT-1) is an IL-6 family cytokine with cytoprotective properties. This preclinical study in rats tested whether CT-1 mitigates cold renal ische...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/TP.0000000000002313
更新日期:2018-10-01 00:00:00
abstract::Tolerogen-specific alloreactivity, in the form of mixed lymphocyte responses and cell mediated lympholysis, was measured in vitro using lymphocytes from mice that received neonatal inoculations of H-2 semiallogeneic hematopoietic cells. It was found that depletion of specific alloreactivity, as detected by these assay...
journal_title:Transplantation
pub_type: 杂志文章
doi:
更新日期:1989-10-01 00:00:00
abstract:BACKGROUND:The beneficial effects of glycemic control on both survival and function of transplanted kidneys in patients with type 1 diabetes mellitus (T1DM) and end-stage renal disease (ESRD) have been recognized. METHODS:Herein, we present the clinical outcome of a single-center pilot trial of islet after kidney (IAK...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/TP.0b013e318166a27b
更新日期:2008-03-27 00:00:00
abstract:BACKGROUND:Antibody-mediated rejection (AMR) remains associated with reduced kidney graft survival and no clear prognostic marker is available. METHODS:We investigated whether donor-specific antibodies (DSA) ability to bind C1q in comparison with AMR C4d status, both indirect signs of complement activation, improve ri...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/TP.0000000000002265
更新日期:2018-11-01 00:00:00