[Show abstract][Hide abstract] ABSTRACT: Aim:
To explore a prophylactic procedure to prevent splenic artery steal syndrome (SASS), as well as a therapeutic intervention to correct it.
Forty-three liver transplant patients were enrolled in a non-randomized controlled trial, with the eligible criterion that the diameter of the splenic artery is more than 5 mm and/or 1.5 times of the diameter of the hepatic artery. The procedure of splenic artery banding was performed in 28 of the 43 patients, with the other 15 patients studied as a control group. SASS and other complications were compared between these two groups. A new therapeutic intervention, temporary incomplete blockade of the splenic artery with a balloon, was performed to treat SASS in this study.
The incidence of SASS was decreased by banding the splenic artery (0/28 vs 5/15, P = 0.006), and the same result was observed in total complications associated with prophylactic procedures (2/28 vs 6/15, P = 0.014). Five patients in the control group developed SASS within 5 d after OLT, 2 of whom were treated by coil embolization of the splenic artery, whereas the other 3 by temporary blockade of the splenic artery. Reappeared or better hepatic arteries with improved systolic amplitude and increased diastolic flow were detected by Doppler ultrasonography in all the 5 patients. Local splenic ischemic necrosis and nonanastomotic biliary stricture were diagnosed respectively in one patient treated by coil embolization, and no collateral complication was detected in patients treated by temporary blockade of the splenic artery.
SASS should be avoided during the operation by banding the splenic artery. Temporary blockade of the splenic artery is a new safe and effective intervention for SASS.
[Show abstract][Hide abstract] ABSTRACT: Aims and background:
Despite elaborate characterization of the risk factors, bladder cancer is still a major epidemiological problem whose incidence continues to rise each year. We aim to investigate the dynamic expression changes between non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC).
The gene expression profile GSE13507 was obtained from the Gene Expression Omnibus, and the R package was used to identify gene expression signatures (GESs) between NMIBC and MIBC. Gene ontology enrichment analysis was performed for GES function analysis. We used miRTarBase and TargetScan to identify the differentially regulated microRNAs, and TfactS to identify transcription factors between NMIBC and MIBC. Bionet was used to identify the differentially expressed subnetwork.
A total of 802 upregulated NMIBC GESs and 668 downregulated MIBC GESs were identified. Functional enrichment analysis revealed that the MIBC GESs were majorly involved in cell cycle and inflammatory response. miR-29c and miR-9 were regarded as key microRNAs in MIBC. SMAD3 in MIBC and SMAD5 and SMAD7 in NMIBC were potential activated transcription factors. In addition, a subnetwork that was considered to capture the differences between MIBC and NMIBC was identified, of which GRB2 and UBC were the hub nodes.
Some key microRNAs, activated transcription factors and hub nodes have been identified in this study, which may be used as potential biomarkers or targets for the diagnosis, treatment and detection of bladder cancer at different stages.
[Show abstract][Hide abstract] ABSTRACT: Several case-control studies and cohort studies have investigated the association between fish intake and renal cancer risk, however, they yielded conflicting results. To our knowledge, a comprehensive assessment of the association between fish consumption and risk of renal cancer has not been reported. Hence, we conducted a systematic literature search and meta-analysis to quantify the association between fish consumption and renal cancer.
A systematic search was performed using the PubMed, Embase, and Cochrane Library Central database for case-control and cohort studies that assessed fish intake and risk of renal cancer. Two authors independently assessed eligibility and extracted data. Fixed-effect and random-effect models were used to estimate summary relative risks (RR) and the corresponding 95% confidence intervals (CIs). Subgroup analyses, sensitivity analysis and cumulative meta-analysis were also performed.
A total of 12 case-control studies and three cohort studies published between 1990 and 2011 were included in the meta-analysis, involving 9,324 renal cancer cases and 608,753 participants. Meta-analysis showed that fish consumption did not significantly affect the risk of renal cancer (RR=0.99, 95% CI [0.92,1.07]). In our subgroup analyses, the results were not substantially affected by study design, region, gender, and confounder adjustments. Furthermore, sensitivity analysis confirmed the stability of results.
The present meta-analysis suggested that there was no significant association between fish consumption and risk of renal cancer. More in-depth studies are warranted to report more detailed results, including stratified results by fish type, preparation method, and gender.
PLoS ONE 11/2013; 8(11):e81939. DOI:10.1371/journal.pone.0081939 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This meta-analysis was undertaken to compare the efficacy and safety of pretransplant treatment with rituximab in sensitized patients receiving kidney transplantation.
PubMed, EMBASE, and Cochrane databases were searched to identify studies that used pretransplantation rituximab in eligible patients. The major outcomes included antibody-mediated rejections (AMR) after kidney transplantation and one-year graft survival rate. The meta-analysis was performed using fixed-effects model.
Seven studies were identified including a total of 589 patients, of whom 312 were treated without rituximab, while 277 were treated with rituximab. In our meta-analysis, patients treated with rituximab had significantly fewer AMR after kidney transplantation [odds ratio (OR) 0.52, 95 % CI 0.28, 0.98, P = 0.04] and higher rate of one-year graft survival rates (OR 3.02, 95 % CI 1.14, 8.02, P = 0.03), indicating that rituximab is effective against acute rejection and enhances graft survival in kidney transplantation. No differences were noted in other efficacy and safety parameters in these two patient groups.
We demonstrated that preinduction with rituximab could significantly improve AMR and graft survival rates in sensitized patients undergoing kidney transplantation. Future prospective controlled studies are warranted to further understand rituximab's role in kidney transplantation.
International Urology and Nephrology 11/2013; 46(6). DOI:10.1007/s11255-013-0599-4 · 1.52 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The human leukocyte antigen-G (HLA-G) has been considered to be an important tolerogeneic molecule playing an essential role in maternal-fetal tolerance, upregulated in the context of transplantation, malignancy, and inflammation, and has been correlated with various clinical outcomes. The aim of this study was to investigate the clinical relevance of the expression of membrane HLA-G (mHLA-G), intracellular HLA-G (iHLA-G), and soluble HLA-G (sHLA-G) in the peripheral blood of live kidney transplant recipients.
We compared the expression of the three HLA-G isoforms in three groups, healthy donors (n=20), recipients with acute rejection (n=19), and functioning transplants (n=30). Flow cytometry was used to detect the expression of mHLA-G and iHLA-G in the T lymphocytes of peripheral blood from subjects in the three groups. Enzyme-linked immunosorbent assays were used to detect sHLA-G in the plasma from the three groups.
There were no significant differences in mHLA-G and intracellular HLA-G among the three groups, but the sHLA-G plasma level was higher in the functioning group than in the acute rejection or healthy group. We found a subset of CD4(+)HLA-G(+) and CD8(+)HLA-G(+) T lymphocytes with low rates of mHLA-G expression in the peripheral blood of kidney transplantation recipients. Intracellular expression of HLA-G was detected in T lymphocytes. However, there was no correlation between acute rejection and the mHLA-G or intracellular HLA-G expression.
sHLA-G was the major isoform in the peripheral blood of live kidney transplant recipients and high sHLA-G levels were associated with allograft acceptance.
Chinese medical journal 07/2013; 126(14):2652-5. DOI:10.3760/cma.j.issn.0366-6999.20122228 · 1.05 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Untreated human cytomegalovirus (CMV) disease (CMVD) is an identified risk factor for reduced rates of patient (and graft) survival, death or retransplantation in kidney transplant recipients due to increased immunological tolerance after transplant. Vitamin D receptor (VDR) gene polymorphisms have an obvious relationship with autoimmune diseases but the relationship between VDR gene polymorphisms and CMVD are not well understood. This study investigated the relationship between VDR FokI and ApaI gene polymorphisms and CMVD, and their value for predicting risk of CMVD.
Ninety-eight kidney transplantation recipients were randomly chosen for which peripheral blood samples and case histories for the first three months after kidney transplantation were obtained. Using polymerase chain reaction-restriction fragment length polymorphisms, 30 recipients were found to be homozygous for the FokI gene (FF), 47 heterozygous (Ff), and 21 were homozygous (ff). Likewise, similar analyses determined that 12 recipients were homozygous for the ApaI gene (AA), 36 heterozygous (Aa), and 50 homozygous (aa). Factors affecting the prognosis of the kidney transplantation were compared for all genotypes by statistical analysis before operation. Infection by CMV for all recipients was detected by immunofluorescence assay to diagnose CMVD.
No statistical significance was observed for the factors affecting the prognosis of the kidney transplantation between both genotypes; however, statistical differences in CMVD among the FokI genotypes were identified. It was determined that the risk of CMVD was significantly increased for recipients of the ff genotype than for other genotypes. There was no statistical significance observed for CMVD among ApaI genotypes.
The recessive f allelic gene of VDR can be regarded as a risk factor of CMVD while FF recipients have lower incidence of CMVD after kidney transplantation. ApaI genotypes showed no relationship with predisposition to CMVD.
Chinese medical journal 10/2012; 125(19):3500-4. DOI:10.3760/cma.j.issn.0366-6999.2012.19.025 · 1.05 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To observe the ratio of Tim-1(+)CD19(+) B cell in the peripheral blood of kidney transplantation recipients and elucidate its functions.
From December 2009 to June 2010, a total of 35 pairs of kidney transplant recipients were selected and divided into 3 groups: healthy donors as control (n = 35), pre-transplantation (n = 35) and post-transplantation (n = 35). The profiles of Tim-1(+)CD19(+) B cell in kidney transplantation donors and recipients were analyzed and sorted by flow cytometry (FCM). Mixed lymphocyte culture (MLC) was carried out between kidney transplantation donors and recipients. After the additions of Tim-1(+)CD19(+) and Tim-1(-)CD19(+) B cells, there were 3 groups: Tim-1(+), Tim-1(-) and blank. Lymphocyte proliferation and inhibition status were evaluated by propidium iodide uptake and Annexin V binding. And the cytokine levels were detected by FCM.
The absolute values of peripheral CD19(+)B cells were (170 ± 90), (202 ± 99), (155 ± 71) cells/µl in the pre-transplantation, post-transplantation and control groups respectively, post-transplantation group were higher than control group (P = 0.0300). The Tim-1(+)CD19(+) cell ratios were (2.20 ± 0.98)%, (35.46 ± 10.66)% and (1.95 ± 0.95)% in three groups. And the differences were statistically significant (both P < 0.01). Tim-1(+)CD19(+) B and Tim-1(-)CD19(+) B cells were added into MLC respectively. The early apoptotic cells of the Tim-1(+) group were higher than those in the Tim-1(-) group [(45.31 ± 12.37)% vs (10.92 ± 2.14)%, P < 0.05] and significantly higher than the blank group [(1.93 ± 0.26)%, P < 0.01]. Late apoptotic and dead cells of the Tim-1(+) group were higher than those in the Tim-1(-) group [(21.32 ± 5.67)% vs (2.32 ± 0.31)%, P < 0.01] and the blank group [(1.27 ± 0.19)%, P < 0.05]. The interleukin 10 levels in MLC supernatant of the Tim-1(+) group were significantly higher than those in the Tim-1(-) group [(5.32 ± 0.37) pg/ml vs (2.46 ± 0.25) pg/ml, P = 0.0001]. However, the interferon-γ levels were lower than those in the Tim-1(-) group [(1.51 ± 0.22) pg/ml vs (4.69 ± 0.32) pg/ml, P = 0.0015].
Present in the peripheral blood of kidney transplantation recipients, Tim-1(+)CD19(+) B cell has the capacity of promoting lymphocytic apoptosis. As a new regulatory subset of B cells, it plays important roles in the immune responses of transplantation.
[Show abstract][Hide abstract] ABSTRACT: In recent years, the Chinese government has made great progress in regulating organ transplant operations. Since 2007, the Chinese Ministry of Health has strictly enforced the authentication program for approval of hospitals to perform organ transplantation.1 Of the more than 600 hospitals that had performed organ transplantations before regulation began, only 163 hospitals now have authentication to perform organ transplantation. Of these, 123 hospitals are approved to perform kidney transplantation, 80 for liver transplantation, 38 for heart transplantation, and 27 for lung transplantation. Quality surveillance and management of transplantations have improved substantially. Hospitals that conduct illegal transplant operations or mismanage organ transplantations are punished with financial penalties or administrative sanctions. For example, 10 hospitals were ordered to improve their transplant program, 7 hospitals had their qualification for transplantation suspended for 3 to 6 months, and 1 was denied qualification.2
JAMA The Journal of the American Medical Association 07/2011; 306(4):434-5. DOI:10.1001/jama.2011.1067 · 35.29 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To explore the efficacy and safety of autologous peripheral blood hematopoietic stem cell transplantation (APBHST) in patients with type 1 diabetes mellitus.
Hematopoietic stem cells were mobilized with cyclophosphamide and granulocyte colony stimulating factor for 16 patients with type 1 diabetes mellitus who admitted to our department during November 2009 to August 2010. And then stem cells were collected from peripheral blood by leukapheresis and cryopreservation. The cells were infused intravenously after conditioning with cyclophosphamide and antithymocyte globulin. To compare the daily dose of exogenous insulin requirements, the serum levels of hemoglobin A1c (HbA1c), C-peptide, islet cell function during the mixed meal tolerance test were measured before and at different times after APBHST. Blood glucose was monitored 7 times a day before and after APBHST. And the adverse effects were recorded during and after APBHST.
The median follow-up was 28 weeks (range: 8 - 44 weeks). Twelve of 16 patients stayed free from insulin at 3 - 20 days post APBHST. And islet cell function greatly improved after APBHST. Four of 16 patients required exogenous insulin but the dosage decreased. And all 4 patients had a poor level of C-peptide before APBHSCT. There were no such severe adverse effects as myelosuppression.
Very encouraging results have been obtained in the patients treated with APBHST. There is definite therapeutic effects and safety in a short term. But further follow-up is necessary to confirm the duration of insulin independence and the mechanisms of action.
[Show abstract][Hide abstract] ABSTRACT: To investigate the role of IL-6/STAT3 pathway in the proliferation of cholangiocytes after liver transplantation and determine whether or not rapamycin (RPM) depresses the regeneration of cholangiocytes by blocking the activation of STAT3.
Rats were randomized into OLT-1 h and OLT-12 h groups (supplied livers preserved for 1 or 12 h), anti-sIL-6R group (rats of the OLT-12 h group injected intravenously with 16.7 µg/kg anti-rat sIL-6R antibody at 1 hour pre-operation and daily post-operation), RPM group (rats of the OLT-12 h group injected intraperitoneally with 0.05 mg/kg RPM for 3 days pre-operation and daily post-operation) and sham group (transverse laparotomy and closure without liver manipulation). At 1, 3, 7, 14 d post-operation, the IL-6 concentration in liver homogenate and cholangiocytes proliferation were detected by ELISA (enzyme linked immunosorbent assay) and histochemistry respectively. The expressions of IL-6 mRNA, phosphorylated-STAT3 and cyclin D1 protein in cholangiocytes were determined by real-time RT-PCR (reverse transcription-polymerase chain reaction) or Western blot. The DNA binding activity of STAT3 was determined by electrophoretic mobility shift assay. The serum concentrations of ALP (alkaline phosphatase) and GGT (γ-glutamyltransferase) were also measured.
The minimal expressions of IL-6, p-STAT3, cyclin D1 and DNA binding activity of STAT3 were detected in OLT-1h group. And a slight increase of IOD (integral optical density) ratio (38 ± 10 and 22 ± 7) indicated a mild cholangiocytes proliferation. The concentrations of GGT were (69 ± 6) U/L, (34 ± 4) U/L and ALP (86 ± 9) U/L, (45 ± 3) U/L. The expression of IL-6 in liver homogenate were (273 ± 20) ng/g, (159 ± 18) ng/g and 0.40 ± 0.04, 0.23 ± 0.04 in cholangiocytes. The expressions of P-STAT3 were 0.420 ± 0.023 and 0.230 ± 0.040 in cholangiocytes and cyclin D1 0.580 ± 0.023 and 0.420 ± 0.015 respectively. Cholangiocytes responded to extended cold preservation with severe bile duct injures and marked increases in IL-6 secretion, p-STAT3 and cyclin D1 protein expression and DNA binding activity of STAT3, followed by compensatory cholangiocytes regeneration. Meanwhile biochemical index and morphology indicated that bile duct injury recovered at 14 d post-operation. The IOD ratios were 38 ± 10 and 22 ± 7 respectively. The expressions of IL-6 were (659 ± 28) and (446 ± 23) ng/g in liver homogenate and 0.73 ± 0.06 and 0.54 ± 0.04 in cholangiocytes. The expression of P-STAT3 were 0.72 ± 0.04 and 0.58 ± 0.06 in cholangiocytes and cyclin D1 0.88 ± 0.04 and 0.74 ± 0.07 respectively. However, anti-sIL-6R inhibited the cholangiocytes proliferation and reduced the expressions of IL-6, STAT3 and cyclin D1. The DNA binding activity of STAT3 with cellular injury and the increases of serum ALP or GGT were also abrogated by the administration of anti-sIL-6R. With similar results, the RPM treatment had insignificant effects on the expression of IL-6.
The IL-6/STAT3 pathway initiates the cholangiocytes regeneration after liver transplantation so as to accelerate the biliary recovery. However RPM represses the cholangiocytes regeneration by inhibiting the STAT3 activation. It may have a negative effect on the healing and recovery of bile ducts in grafts with extended cold preservation.
[Show abstract][Hide abstract] ABSTRACT: Invasive kidney biopsy is a priority diagnostic method for the acute rejection after renal transplantation for the past decades. However, no effective and noninvasive assay for predicting the severity of acute rejection is in wide use at present. This study was designed to investigate the predictive value of programmed death 1 (PD-1) mRNA for acute rejection after renal transplantation with real-time reverse transcriptase polymerase chain reaction (RT-PCR). A noninvasive diagnostic method has been expected to replace the traditional kidney biopsy for the diagnosis of acute rejection and prediction of the outcome after kidney transplantation.
The whole blood samples from 19 subjects with acute rejection, 20 subjects with delayed graft function (DGF) and 21 subjects with stable recipients after kidney transplantation in a single kidney transplantation center between 2006 and 2009 were collected. The messenger RNA (mRNA) of PD-1 was analyzed with real-time RT-PCR. The associations of PD-1 mRNA levels with acute rejection and disease severity were investigated.
The log-transformed ratio of PD-1 mRNA to GAPDH mRNA was higher in peripheral blood mononuclear cell (PBMC) from the group with acute rejection (4.52 ± 1.1) than that from the group with DGF (1.12 ± 0.6) or the group with normal biopsy results (0.7 ± 0.4) (P < 0.01, by the Kruskal-Wallis test). PD-1 mRNA levels were correlated with serum creatinine levels measured at the time of biopsy in the acute rejection group (Spearman's correlation coefficient, r = 0.81, P = 0.03), but not in the group with DGF or the group with normal biopsy results. PD-1 mRNA levels identified subjects at risk for graft failure within six months after the incident episode of acute rejection.
Our data suggest that PD-1 status may be a new predictor of acute rejection and the levels of PD-1 mRNA in whole blood cells may positively correlate with the severity of acute rejection after renal transplantation. Meanwhile, the data provide the rational for interfering into the PD-1/PD-L1 as a novel therapy against the acute rejection after renal transplantation in clinical settings.
Chinese medical journal 03/2011; 124(5):674-8. DOI:10.3760/cma.j.issn.0366-6999.2011.05.007 · 1.05 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To find whether the up-regulation of soluble human leucocyte antigen-G5 (sHLA-G5) levels is a new function mechanism of anti-interleukin-2 receptors (anti-IL-2R) monoclonal antibody treatment in kidney transplantation.
A total of 215 recipients at our centre from January 2006 to December 2007 were divided into antibody use group (n = 141) and antibody non-use group (n = 74) and another healthy group (n = 69). The sHLA-G5 level in peripheral blood was detected by enzyme-linked immunosorbent assay (ELISA). And the expression of HLA-G5 was confirmed by Western blot and Real-time polymerase chain reaction (PCR).
sHLA-G5 levels was (56 ± 30) µg/L in using anti-IL-2 receptor monoclonal antibody before transplantation, It was higher than that before use antibody [(34 ± 20) µg/L], also higher than healthy group [(35 ± 17) µg/L] and antibody non-use group [(36 ± 19) µg/L, P < 0.05, respectively]. At Day 1, Day 4, Week 1, Week 2 post-transplantation, the level of sHLA-G5 of recipients with antibody use was significantly higher than that of those with antibody non-use. The values were as follows: (95 ± 35) µg/L vs (54 ± 16) µg/L, (131 ± 24) µg/L vs (75 ± 22) µg/L, (167 ± 44) µg/L vs (62 ± 17) µg/L, (172 ± 35) µg/L vs (45 ± 16) µg/L (all P < 0.01). And the results of Western blot and RT-PCR corresponded to those of ELISA.
The preoperative use of first dose of anti-IL-2R monoclonal antibodies results in the up-regulated level of sHLA-G5. Thus it is beneficial for protecting the kidney survival and reducing the risks of acute rejection.
[Show abstract][Hide abstract] ABSTRACT: To establish ELISA method for quantitate the concentration of cystatin C (cys C) and to monitor the renal function of patients before and after renal transplantation.
Hybridomas secreting monoclonal antibodies (mAbs) against human cys C were produced and sandwich ELISA kit for quantitatively detecting cys C was established. Then the concentrations of serum cystatin C (Scys C) and urine cystatin C (Ucys C) from normal controls and 23 patients undergoing renal transplantation were detected and their relationship with serum creatinine (SCR) was analyzed.
Seven hybridomas secreting anti-cys C mAbs were obtained. The sensitivity of the established ELISA kit reached 0.1 μg/L. The concentrations of Scys C and Ucys C of normal healthy controls were in accordance with other report. High correlations between Scys C or Ucys C and the level of SCR were observed (P<0.01). Rapid decline of Scys C and Ucys C concentrations was consistent with the decrease of SCR in the patients with normal course (NC) recovery after renal transplantation. However, Ucys C kept higher level within two weeks after the operation in patients with AR until the day 21. In patients with DGF, higher levels of Scys C, Ucys C and SCR were sustained within four weeks after renal transplantation.
The sensitive ELISA kit for detection of cys C has been established. Importantly, there are the persistently high levels of Scys C and Ucys C in patients with AR or DGF, which can be used as a novel indicator for monitoring renal function after renal transplantation.
Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology 11/2010; 26(11):1140-2.
[Show abstract][Hide abstract] ABSTRACT: to study the feasibility of human leucocyte antigen-G (HLA-G) as a post-transplantation prognostic biomarker and discuss the correlation of its receptor expression and the mechanisms.
a total of 215 recipients in our centre from February 2006 to June 2008 were divided into stable kidney function group (n = 173) and acute rejection group (n = 42). The soluble human leucocyte antigen-G5 (sHLA-G5) level in peripheral plasma was detected by ELISA. And the HLA-G receptor ILT-2, KIR2DL4 on T, B, NK lymphocytes were analyzed by flow cytometry (FCM). The sHLA-G5 cutoff level by ROC curve was employed to predict the events of acute post-transplantation rejection. And regression analysis was used to determine the association of sHLA-G5 with acute rejection.
an optimal cutoff value of 139.0 microg/L could be defined for sHLA-G5 (sensitivity: 63.6%, specificity: 82.1%, AUC: 0.780). Binary regression analysis showed that sHLA-G5 played an independent role on acute rejection (P = 0.019, OR = 0.039, 95%CI: 2.091 - 5.661). The rate of HLA-G receptor ILT-2 on CD4(+)T cell, CD8(+)T cell and B cell in acute rejection group was statistically lower than that in stable kidney function group (21% ± 7% vs 52% ± 17%, 23% ± 6% vs 39% ± 16%, 21% ± 7% vs 39% ± 16%, all P < 0.05). The expression of KIR2DL4 on NK cells in acute rejection group was statistically lower than that in stable kidney function group (31% ± 10%vs 57% ± 21%, P < 0.05).
sHLA-G5 level may be predicted for acute rejection with a high sensitivity and specificity. The up-regulated expression of ILT-2 and KIR2DLT may contribute to immunology tolerance in peripheral circulation.
[Show abstract][Hide abstract] ABSTRACT: Extracorporeal photopheresis (ECP) is an effective immunomodulatory therapy and has been demonstrated to be beneficial for graft-vs-host disease and solid-organ allograft rejection. ECP involves reinfusion of a patient's autologous peripheral blood leukocytes treated ex vivo with 8-methoxypsoralen and UVA light radiation (PUVA). Previous studies focused only on ECP treatment of recipient immune cells. Our study is the first to extend the target of ECP treatment to donor immune cells. The results of in vitro co-culture experiments demonstrate uptake of donor PUVA-treated splenic lymphocytes (PUVA-SPs) by recipient immature dendritic cells (DCs). Phagocytosis of donor PUVA-SPs does not stimulate phenotype maturation of recipient DCs. In the same co-culture system, donor PUVA-SPs enhanced production of interleukin-10 and interferon-gamma by recipient DCs and impaired the subsequent capability of recipient DCs to stimulate recipient naïve T cells. Phagocytosis of donor PUVA-SP (PUVA-SP DCs) by recipient DCs shifted T-cell responses in favor of T helper 2 cells. Infusion of PUVA-SP DCs inhibited cardiac allograft rejection in an antigen-specific manner and induced CD4(+)CD25(high)Foxp3(+) regulatory T cells. In conclusion, PUVA-SP DCs simultaneously deliver the donor antigen and the regulatory signal to the transplant recipient, and thus can be used to develop a novel DC vaccine for negative immune regulation and immune tolerance induction.
Biochemical and Biophysical Research Communications 05/2010; 395(4):540-6. DOI:10.1016/j.bbrc.2010.04.062 · 2.30 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Cholangiocyte proliferation is necessary for biliary recovery from cold ischemia and reperfusion injury (CIRI), but there are few studies on its intracellular mechanism. In this process, the role of rapamycin, a new immunosuppressant used in liver transplantation, is still unknown. In order to determine whether rapamycin can depress cholangiocyte regeneration by inhibiting signal transducer and activator of transcription 3 (STAT3) activation, rapamycin (0.05 mg/kg) was administered to rats for 3 days before orthotopic liver transplantation. The results indicated that cholangiocytes responded to extended cold preservation (12 hours) with severe bile duct injures, marked activation of the interleukin-6 (IL-6)/STAT3 signal pathway, and increased expression of cyclin D1 until 7 days after transplantation, and this was followed by compensatory cholangiocyte regeneration. However, rapamycin treatment inhibited STAT3 activation and resulted in decreased cholangiocyte proliferation and delayed biliary recovery after liver transplantation. On the other hand, rapamycin showed no effect on the expression of IL-6. We conclude that the IL-6/STAT3 signal pathway is involved in initiating cholangiocytes to regenerate and repair CIRI. Rapamycin represses cholangiocyte regeneration by inhibiting STAT3 activation, which might have a negative effect on the healing and recovery of bile ducts in grafts with extended cold preservation. Insights gained from this study will be helpful in designing therapy using rapamycin in clinical patients after liver transplantation.
[Show abstract][Hide abstract] ABSTRACT: To investigate the effect of recipient dendritic cells (DC) loaded with PUVA-treated donor splenic lymphocytes (PUVA-SP) on CD4(+) CD25(+) regulatory T cells (Treg) and the survival time of cardiac allograft in rats.
Cardiac allografts from DA donor rats were transplanted into LEW recipient rats. Donor splenic lymphocytes were treated with 8-methoxypsoralen plus UVA irradiation (PUVA). Recipient bone marrow-derived DCs were co-cultured with PUVA-treated donor splenic lymphocytes (PUVA-SP) and the phenotype of the treated DCs was analyzed with flow cytometry. Seven days before transplantation, recipients were given infusion of recipient DCs loaded with PUVA-treated donor splenic lymphocytes (PUVA-SP DC) through the peripheral vein. The cardiac allograft survival time was evaluated by palpation every day. The frequency of CD4(+)CD25(+) T cells and CD4(+) CD25(high) T cells and their Foxp3 expression were analyzed using flow cytometry. Fourteen days after transplantation, T lymphocytes of the recipient rats receiving PUVA-SP DC were transferred to the normal LEW rats. The delayed type hypersensitivity (DTH) of the transferred LEW rats to the donor DA rats antigen then was measured.
After co-cultured with PUVA-SP, recipient DCs still maintained an immature phenotype with low levels of MHC II, CD80 and CD86. The injection of PUVA-SP DCs significantly increased the frequencies of CD4(+)CD25(+) T cells and CD4(+) CD25(high) T cells and the expression of Foxp3 in the peripheral blood, and prolonged the allograft survival time. The donor antigen specific hyporesponsiveness could be transferred to normal LEW rats through adoptive transfusion.
PUVA-SP DCs effectively up-regulate CD4(+) CD25(+) Foxp3(+) Treg and induce donor antigen specific hyporesponsiveness, thus prolonging the allograft survival time.
Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology 01/2010; 26(1):13-7.