Cell-mediated Immunomodulation of Chemokine Receptor 7–expressing Porcine Sertoli Cells in Murine Heterotopic Heart Transplantation
Autor: | Byoung Chol Oh, Hong Gook Lim, Hak Mo Lee, Jeong Ryul Lee |
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Rok vydání: | 2009 |
Předmět: |
Male
Pulmonary and Respiratory Medicine Receptors CCR7 Transplantation Heterotopic Swine medicine.medical_treatment Transplantation Heterologous Bone Marrow Cells chemical and pharmacologic phenomena C-C chemokine receptor type 7 Lymphocyte proliferation Lymphocyte Activation Mice Chemokine receptor Immune system Splenocyte Animals Immunologic Factors Transplantation Homologous Medicine Mice Inbred BALB C Transplantation Sertoli Cells Reverse Transcriptase Polymerase Chain Reaction business.industry Immunosuppression Dendritic Cells Skin Transplantation Mice Inbred C57BL Cytokine Animals Newborn Immunology Heart Transplantation Female Surgery Lymphocyte Culture Test Mixed Cardiology and Cardiovascular Medicine business Spleen |
Zdroj: | The Journal of Heart and Lung Transplantation. 28:72-78 |
ISSN: | 1053-2498 |
DOI: | 10.1016/j.healun.2008.09.011 |
Popis: | Background Sertoli cells (SC) have immunomodulative properties, and chemokine receptor 7 (CCR7) can optimize the systemic immunomodulatory effect by guiding SC from the periphery to the secondary lymphoid organs. Methods The effect of immortalized neonatal porcine SC (NPSCi) was evaluated by analysis of cytokine levels. Hyporesponsiveness to donor cells was determined by MLC and analysis of splenocyte phenotypes using a murine allogeneic skin graft model. The effect of CCR7-expressing NPSCi (NPSCi-CCR7) combined with cobra venom factor (CVF) was evaluated using a heterotopically transplanted murine allogeneic heart model. Results Expression of immune cytokines was markedly modulated by NPSCi. The lymphocyte proliferation and splenocyte phenotypes were significantly suppressed by NPSCi-CCR7. Although pre-transplantation of NPSCi or NPSCi-CCR7 did not prolong graft survival of allogeneic cardiac grafts, CVF treatment facilitated pre-transplantation of NPSCi-CCR7 to prolong survival of allogeneic cardiac grafts (25.5 ± 7.05 vs 9.5 ± 0.58 days, p Conclusions NPSCi may be used as a powerful immunomodulatory tool, and our strategy to traffic NPSCi to lymphoid organs using CCR7 optimizes the systemic immunomodulatory effect in vivo. With the help of initial immunosuppression for humoral mechanisms using CVF, the host immune response against allogeneic cardiac grafts can be effectively ameliorated by immunomodulation of the cellular mechanism with NPSCi-CCR7. |
Databáze: | OpenAIRE |
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