Intrasplenic Liver Parenchymal Cells in Conjunction with Low-Dose Rapamycin and Cyclosporine Induce a Unique and Specific Prolongation of Rat Cardiac and Small Bowel Allograft Survival
These experiments investigated the immunosuppressive properties of liver tissue. Brown Norway (BN; RT1 n ) rat heart allografts survived in untreated control Wistar Furth (WFu; RTl u ) rat recipients for 6.2 ± 1.5 days, while allografts in animals that received rapamycin (RAPA) 0.0075 mg/kg/day and...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publishing
1998-05-01
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| Series: | Cell Transplantation |
| Online Access: | https://doi.org/10.1177/096368979800700303 |
| _version_ | 1811289363481362432 |
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| author | Michael J. Boyle M.D. Vano Baghdassarian Stanislaw M. Stepkowski Lynette J. Dumble Barry D. Kahan |
| author_facet | Michael J. Boyle M.D. Vano Baghdassarian Stanislaw M. Stepkowski Lynette J. Dumble Barry D. Kahan |
| author_sort | Michael J. Boyle M.D. |
| collection | DOAJ |
| description | These experiments investigated the immunosuppressive properties of liver tissue. Brown Norway (BN; RT1 n ) rat heart allografts survived in untreated control Wistar Furth (WFu; RTl u ) rat recipients for 6.2 ± 1.5 days, while allografts in animals that received rapamycin (RAPA) 0.0075 mg/kg/day and cyclosporine (CsA) 0.375 mg/kg/day delivered for 14 days by continuous intravenous infusion (civi) using osmotic pumps in conjunction with intrasplenic (i.s.) saline survived to 18.4 ± 1.3 days. i.s. addition of 3 M-KCl extracted BN hepatic antigen or unpurified BN hepatocytes (liver parenchymal cells—5 × 10 7 /kg), which exhibited a 4.8% class II antigen expression, and which alone failed to prolong allograft survival (MST = 6.0 ± 1.4 days), increased heart allograft survival to 25.3 ± 2.3 and 27.2 ± 1.9 days, respectively (p < 0.01). Hepatocyte purification using Dynabeads and Percoll reduced class II expression to 0.9% and increased allograft survival to 32.8 ± 1.6 days (p < 0.01). In contrast, the effect of 5 × 10 8 /kg BN erythrocytes, exhibiting only 0.1% class II expression, was much less (23.8 ± 1.9 days). Administration i.s. of BN splenocytes or nonparenchymal liver cells, demonstrated by flow cytometry to exhibit a 47.3 or 55.1% expression of class II antigen, respectively, failed to induce any significant increase in allograft survival (18.4 ± 4.6 and 19.4 ± 0.5 days, respectively). Survival of BN rat small bowel allografts was increased in Lewis (LEW; RTl 1 ) rat recipients treated with RAPA, CsA, and unfractionated BN hepatocytes from 10.2 ± 1.9 to 21.2 ± 1.5 days. Pretreatment with i.s. BN hepatocytes, 14 days prior to harvesting, reduced WFu lymphocyte responses to allogeneic stimulation with BN or ACI spleen cells by 75 and 70%, respectively. Addition of 1 × 10 5 unpurified donor-specific BN or third-party Buffalo (BUF; RTl b ) hepatocytes, but not supernatant, to the responder wells of MLCs resulted in a 61 and 40% suppression, respectively, of the WFu lymphocyte response induced by BN allogeneic stimulation. These findings suggest that while class I MHC expression has a significant role to play in exerting the immunosuppressive effects of hepatocytes, other influences more specific to liver may also prevail. |
| first_indexed | 2024-04-13T03:53:33Z |
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| institution | Directory Open Access Journal |
| issn | 0963-6897 1555-3892 |
| language | English |
| last_indexed | 2024-04-13T03:53:33Z |
| publishDate | 1998-05-01 |
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| series | Cell Transplantation |
| spelling | doaj.art-b3745370ad6d4314aa612a9ea9127ba12022-12-22T03:03:42ZengSAGE PublishingCell Transplantation0963-68971555-38921998-05-01710.1177/096368979800700303Intrasplenic Liver Parenchymal Cells in Conjunction with Low-Dose Rapamycin and Cyclosporine Induce a Unique and Specific Prolongation of Rat Cardiac and Small Bowel Allograft SurvivalMichael J. Boyle M.D.0Vano Baghdassarian1Stanislaw M. Stepkowski2Lynette J. Dumble3Barry D. Kahan4Department of Surgery, The University of Texas Medical School at Houston, Houston, TX 77030, USADepartment of Surgery, The University of Texas Medical School at Houston, Houston, TX 77030, USADepartment of Surgery, The University of Texas Medical School at Houston, Houston, TX 77030, USADepartment of Surgery, The University of Texas Medical School at Houston, Houston, TX 77030, USADepartment of Surgery, The University of Texas Medical School at Houston, Houston, TX 77030, USAThese experiments investigated the immunosuppressive properties of liver tissue. Brown Norway (BN; RT1 n ) rat heart allografts survived in untreated control Wistar Furth (WFu; RTl u ) rat recipients for 6.2 ± 1.5 days, while allografts in animals that received rapamycin (RAPA) 0.0075 mg/kg/day and cyclosporine (CsA) 0.375 mg/kg/day delivered for 14 days by continuous intravenous infusion (civi) using osmotic pumps in conjunction with intrasplenic (i.s.) saline survived to 18.4 ± 1.3 days. i.s. addition of 3 M-KCl extracted BN hepatic antigen or unpurified BN hepatocytes (liver parenchymal cells—5 × 10 7 /kg), which exhibited a 4.8% class II antigen expression, and which alone failed to prolong allograft survival (MST = 6.0 ± 1.4 days), increased heart allograft survival to 25.3 ± 2.3 and 27.2 ± 1.9 days, respectively (p < 0.01). Hepatocyte purification using Dynabeads and Percoll reduced class II expression to 0.9% and increased allograft survival to 32.8 ± 1.6 days (p < 0.01). In contrast, the effect of 5 × 10 8 /kg BN erythrocytes, exhibiting only 0.1% class II expression, was much less (23.8 ± 1.9 days). Administration i.s. of BN splenocytes or nonparenchymal liver cells, demonstrated by flow cytometry to exhibit a 47.3 or 55.1% expression of class II antigen, respectively, failed to induce any significant increase in allograft survival (18.4 ± 4.6 and 19.4 ± 0.5 days, respectively). Survival of BN rat small bowel allografts was increased in Lewis (LEW; RTl 1 ) rat recipients treated with RAPA, CsA, and unfractionated BN hepatocytes from 10.2 ± 1.9 to 21.2 ± 1.5 days. Pretreatment with i.s. BN hepatocytes, 14 days prior to harvesting, reduced WFu lymphocyte responses to allogeneic stimulation with BN or ACI spleen cells by 75 and 70%, respectively. Addition of 1 × 10 5 unpurified donor-specific BN or third-party Buffalo (BUF; RTl b ) hepatocytes, but not supernatant, to the responder wells of MLCs resulted in a 61 and 40% suppression, respectively, of the WFu lymphocyte response induced by BN allogeneic stimulation. These findings suggest that while class I MHC expression has a significant role to play in exerting the immunosuppressive effects of hepatocytes, other influences more specific to liver may also prevail.https://doi.org/10.1177/096368979800700303 |
| spellingShingle | Michael J. Boyle M.D. Vano Baghdassarian Stanislaw M. Stepkowski Lynette J. Dumble Barry D. Kahan Intrasplenic Liver Parenchymal Cells in Conjunction with Low-Dose Rapamycin and Cyclosporine Induce a Unique and Specific Prolongation of Rat Cardiac and Small Bowel Allograft Survival Cell Transplantation |
| title | Intrasplenic Liver Parenchymal Cells in Conjunction with Low-Dose Rapamycin and Cyclosporine Induce a Unique and Specific Prolongation of Rat Cardiac and Small Bowel Allograft Survival |
| title_full | Intrasplenic Liver Parenchymal Cells in Conjunction with Low-Dose Rapamycin and Cyclosporine Induce a Unique and Specific Prolongation of Rat Cardiac and Small Bowel Allograft Survival |
| title_fullStr | Intrasplenic Liver Parenchymal Cells in Conjunction with Low-Dose Rapamycin and Cyclosporine Induce a Unique and Specific Prolongation of Rat Cardiac and Small Bowel Allograft Survival |
| title_full_unstemmed | Intrasplenic Liver Parenchymal Cells in Conjunction with Low-Dose Rapamycin and Cyclosporine Induce a Unique and Specific Prolongation of Rat Cardiac and Small Bowel Allograft Survival |
| title_short | Intrasplenic Liver Parenchymal Cells in Conjunction with Low-Dose Rapamycin and Cyclosporine Induce a Unique and Specific Prolongation of Rat Cardiac and Small Bowel Allograft Survival |
| title_sort | intrasplenic liver parenchymal cells in conjunction with low dose rapamycin and cyclosporine induce a unique and specific prolongation of rat cardiac and small bowel allograft survival |
| url | https://doi.org/10.1177/096368979800700303 |
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