The Experts below are selected from a list of 72 Experts worldwide ranked by ideXlab platform

Michel Ovize - One of the best experts on this subject based on the ideXlab platform.

  • link between immune cell infiltration and mitochondria induced cardiomyocyte death during acute Cardiac Graft Rejection
    American Journal of Transplantation, 2006
    Co-Authors: Ludovic Gomez, O Raisky, Lara Chalabreysse, C Verschelde, N Bonnefoyberard, Michel Ovize
    Abstract:

    Acute Cardiac Graft Rejection (ACGR) is associated with cardiomyocyte apoptosis. We investigated the respective role of the Fas/FasL and mitochondrial permeability transition pore (mPTP) pathways in cardiomyocyte apoptosis accompanying ACGR. Heterotopic Cardiac transplantations were performed in 7–9-week old C57BL6 or C3H mice. Wild type or Fas-deficient (lpr) mice underwent syngeneic (GS) or allogeneic (GA) transplantation, and received either saline or NIM811, a specific inhibitor of the mPTP. At day 5, we assessed ACGR by histology, cardiomyocyte apoptosis by caspase-3 activity and cytochrome c release, Ca2+-induced mPTP opening by a potentiometric approach, and expression of Fas, FasL, TNFα, perforin, granzyme using RT-PCR. Myocardial infiltration of CD8+ T lymphocytes was performed by immunohistochemistry. Allogenic transplantation increased infiltration of inflammatory cells, upregulated FasL, perforin, granzyme, and TNFα, favored Ca2+-induced mPTP opening and increased caspase-3 activity and cytochrome c release in WT Grafts. NIM811, but not Fas-deficiency, significantly reduced all these effects. NIM811 also limited infiltration of CD8+ into WT and lpr transplants. These data suggest that the mPTP pathway plays a major role in cardiomyocyte apoptosis associated with ACGR. Inhibition of mPTP opening may attenuate cardiomyocyte apoptosis either directly or indirectly via a limitation of CD8+ T-cell activation.

  • Mitochondrial permeability transition in cardiomyocyte apoptosis during acute Graft Rejection
    American Journal of Transplantation, 2004
    Co-Authors: Olivier Raisky, L. Gomez, L. Chalabreysse, O. Gateau-roesch, Joseph Loufouat, Françoise Thivolet-bejui, J. Ninet, Michel Ovize
    Abstract:

    Evidence indicates that acute Cardiac Graft Rejection is associated with cardiomyocyte apoptosis. Mitochondrial permeability transition (MPT) induces apoptotic cell death. We sought to determine whether MPT might play a role in cardiomyocyte apoptosis in the rat model of heterotopic Cardiac transplantation. Syngenic and allogenic transplantations were performed, and both native and Grafted hearts were harvested 3 or 5 d after transplantation for detection of acute Rejection, assessment of Ca2+-induced MPT, and myocardial apoptosis by TUNEL staining and caspase 3 activity. Allogenic Grafts developed severe acute Rejection at day 5 with concomitant cardiomyocyte apoptosis (apoptotic index: 7.1 +/- 1.0% vs. 1.0 +/- 0.2% in syngenic hearts, and caspase 3 activity: 38 +/- 25 vs. 5 +/- 9 nmol/mg, in allogenic vs. syngenic Grafts, respectively). At day 5, Ca2+-induced MPT was dramatically altered in allogenic when compared with syngenic Grafts (mean Ca2+ overload averaged 0 +/- 20 vs. 280 +/- 30 muM in allogenic and syngenic Grafts, respectively). NIM811, a nonimmunosuppressive derivative of cyclosporin A (CsA), that specifically inhibits the MPT pore, did not alter acute Rejection, but significantly delayed Ca2+-induced MPT pore opening, attenuated caspase 3 activity and cardiomyocyte apoptosis in allogenic Grafts. This suggests that mitochondrial permeability transition pore opening may play an important role in cardiomyocyte apoptosis associated with acute Cardiac Graft Rejection.

Leendert C Paul - One of the best experts on this subject based on the ideXlab platform.

  • anti integrin lfa 1 vla 4 and mac 1 antibody treatment and acute Cardiac Graft Rejection in the rat
    Transplant International, 1996
    Co-Authors: Leendert C Paul, Allen W Davidoff, Hallgrimur Benediktsson, Thomas B Issekutz
    Abstract:

    Cell adhesion molecules mediate interactions with other cells and extracellular matrix, control cell infiltration in sites of inflammation, and regulate cell activation. Previous studies have shown that treatment of rat Cardiac transplant recipients with a combination of antibodies against the T-cell integrins LFA-1 and VLA-4 gave a modest prolongation of Graft survival. Current experiments were designed to examine the effect of blocking Mac-1, an important monocyte adhesion receptor and mediator of monocyte migration, together with anti-LFA-1 and anti-VLA-4 antibodies on Cardiac Graft survival and on the Graft Rejection pattern. The anti-Mac-1, CD11b-specific antibody OX-42 did not affect Graft survival time although it did decrease the Graft infiltration by rounded, ED-2-positive macrophages.

Yan Chen - One of the best experts on this subject based on the ideXlab platform.

  • adiponectin mediated mhc class ii mismatched Cardiac Graft Rejection in mice is il 4 dependent
    PLOS ONE, 2012
    Co-Authors: Julia Y S Tsang, Jiao Peng, Y K Chan, Jiang Zhu, Vincent Chi Hang Lui, Jonathan R Lamb, Paul K H Tam, Yan Chen
    Abstract:

    Background: Adiponectin regulates glucose and fatty-acid metabolism but its role in chronic Graft Rejection mediated by Th2 cytokines remains ill-defined. Methodology/Principal Findings: Wild type and adiponectin-null mice were used as Graft recipients in mouse MHC class II disparate Cardiac transplantation (bm12 toB6) and the Graft Rejection was monitored. In adiponectin-null mice we observed that the cellular infiltrate of eosinophils, CD4 + and CD8 + T cells was reduced in Grafts compared to the controls as was collagen deposition and vessel occlusion. A similar outcome was observed for skin transplants except that neutrophil infiltration was increased. Low levels of IL-4 were detected in the Grafts and serum. The effect of adiponectin signaling on IL4 expression was further investigated. Treatment with AMPK and p38 MAPK inhibitors blocked adiponectin enhanced T cell proliferation in mixed lymphocyte reactions. Inhibition of AMPK reduced eosinophil infiltration in skin Grafts in wild type recipients and in contrast AMPK activation increased eosinophils in adiponectin-null recipients. The addition of adiponectin increased IL-4 production by the T cell line EL4 with augmented nuclear GATA-3 and phospho-STAT6 expression which were suppressed by knockdown of adiponectin receptor 1 and 2. Conclusions: Our results demonstrate a direct effect of adiponectin on IL-4 expression which contributes to Th2 cytokine mediated Rejection in mouse MHC class II histoincompatible transplants. These results add to our understanding of the interrelationship of metabolism and immune regulation and raise the possibility that AMPK inhibitors may be beneficial in selected types of Rejection.

Thomas B Issekutz - One of the best experts on this subject based on the ideXlab platform.

  • anti integrin lfa 1 vla 4 and mac 1 antibody treatment and acute Cardiac Graft Rejection in the rat
    Transplant International, 1996
    Co-Authors: Leendert C Paul, Allen W Davidoff, Hallgrimur Benediktsson, Thomas B Issekutz
    Abstract:

    Cell adhesion molecules mediate interactions with other cells and extracellular matrix, control cell infiltration in sites of inflammation, and regulate cell activation. Previous studies have shown that treatment of rat Cardiac transplant recipients with a combination of antibodies against the T-cell integrins LFA-1 and VLA-4 gave a modest prolongation of Graft survival. Current experiments were designed to examine the effect of blocking Mac-1, an important monocyte adhesion receptor and mediator of monocyte migration, together with anti-LFA-1 and anti-VLA-4 antibodies on Cardiac Graft survival and on the Graft Rejection pattern. The anti-Mac-1, CD11b-specific antibody OX-42 did not affect Graft survival time although it did decrease the Graft infiltration by rounded, ED-2-positive macrophages.

Akihiko Yoshimura - One of the best experts on this subject based on the ideXlab platform.

  • prevention of allogeneic Cardiac Graft Rejection by transfer of ex vivo expanded antigen specific regulatory t cells
    PLOS ONE, 2014
    Co-Authors: Fumika Takasato, Rimpei Morita, Takashi Schichita, Takashi Sekiya, Yasuhide Morikawa, Tatsuo Kuroda, Masanori Niimi, Akihiko Yoshimura
    Abstract:

    The rate of Graft survival has dramatically increased using calcineurin inhibitors, however chronic Graft Rejection and risk of infection are difficult to manage. Induction of alloGraft-specific regulatory T-cells (Tregs) is considered an ideal way to achieve long-term tolerance for alloGrafts. However, efficient in vitro methods for developing alloGraft-specific Tregs which is applicable to MHC full-mismatched Cardiac transplant models have not been established. We compared antigen-nonspecific polyclonal-induced Tregs (iTregs) as well as antigen-specific iTregs and thymus-derived Tregs (nTregs) that were expanded via direct and indirect pathways. We found that iTregs induced via the indirect pathway had the greatest ability to prolong Graft survival and suppress angiitis. Antigen-specific iTregs generated ex vivo via both direct and indirect pathways using dendritic cells from F1 mice also induced long-term enGraftment without using MHC peptides. In antigen-specific Treg transferred models, activation of dendritic cells and alloGraft-specific CTL generation were suppressed. The present study demonstrated the potential of ex vivo antigen-specific Treg expansion for clinical cell-based therapeutic approaches to induce lifelong immunological tolerance for allogeneic Cardiac transplants.