Hyperthermic Preconditioning Protects Pig Islet Grafts from Early Inflammation but Enhances Rejection in Immunocompetent Mice
The induction of heat shock proteins (HSP) protects isolated islet cells against the cytotoxicity of inflammatory mediators in vitro. Very little information is available about the effect of HSP overexpression on function of preconditioned islet grafts. The present study investigated the function of...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2003-11-01
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| Series: | Cell Transplantation |
| Online Access: | https://doi.org/10.3727/000000003771000200 |
| _version_ | 1818232366669234176 |
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| author | Daniel Brandhorst Ph.D. Heide Brandhorst Vidya Kumarasamy Adel Maataoui Alexandra Alt Mathias D. Brendel Reinhard G. Bretzel |
| author_facet | Daniel Brandhorst Ph.D. Heide Brandhorst Vidya Kumarasamy Adel Maataoui Alexandra Alt Mathias D. Brendel Reinhard G. Bretzel |
| author_sort | Daniel Brandhorst Ph.D. |
| collection | DOAJ |
| description | The induction of heat shock proteins (HSP) protects isolated islet cells against the cytotoxicity of inflammatory mediators in vitro. Very little information is available about the effect of HSP overexpression on function of preconditioned islet grafts. The present study investigated the function of heat-exposed pig islets after transplantation into immunocompetent mice in comparison with in vitro resistance against inflammatory mediators. Pig islets were preconditioned at 43°C or sham treated prior to subcapsular transplantation into diabetic C57/Bl6j mice. Nondiabetic mice simultaneously receiving preconditioned and control islets were subjected to bilateral nephrectomy for determination of pig insulin. Resistance against H 2 O 2 , NO, human Il-1β, IFN-γ, or TNF-α was assessed by trypan blue exclusion and insulin determination. Heat-induced protein expression was confirmed by Western blot analysis. Graft preconditioning increased resistance against H 2 O 2 , NO, or cytokines (p < 0.05) but decreased survival in nondiabetic mice (p < 0.05) and function in diabetic mice (p < 0.01). Upregulation of caspase-3 activity as well as Bax, Fas, FasL, and DFF expression (p < 0.05) indicated simultaneous induction of apoptosis. The coexpression of HSP and proapoptotic proteins reveals the dual character of the stress response simultaneously starting mechanisms for protection and apoptosis. In vitro assays seem to reflect only insufficiently the situation of islets after transplantation. |
| first_indexed | 2024-12-12T11:05:09Z |
| format | Article |
| id | doaj.art-ea7b4a317c8e44f5b7eb74da119fa440 |
| institution | Directory Open Access Journal |
| issn | 0963-6897 1555-3892 |
| language | English |
| last_indexed | 2024-12-12T11:05:09Z |
| publishDate | 2003-11-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Cell Transplantation |
| spelling | doaj.art-ea7b4a317c8e44f5b7eb74da119fa4402022-12-22T00:26:26ZengSAGE PublishingCell Transplantation0963-68971555-38922003-11-011210.3727/000000003771000200Hyperthermic Preconditioning Protects Pig Islet Grafts from Early Inflammation but Enhances Rejection in Immunocompetent MiceDaniel Brandhorst Ph.D.0Heide Brandhorst1Vidya Kumarasamy2Adel Maataoui3Alexandra Alt4Mathias D. Brendel5Reinhard G. Bretzel6Third Medical Department, Justus-Liebig-University, Giessen, GermanyThird Medical Department, Justus-Liebig-University, Giessen, GermanyThird Medical Department, Justus-Liebig-University, Giessen, GermanyThird Medical Department, Justus-Liebig-University, Giessen, GermanyThird Medical Department, Justus-Liebig-University, Giessen, GermanyThird Medical Department, Justus-Liebig-University, Giessen, GermanyThird Medical Department, Justus-Liebig-University, Giessen, GermanyThe induction of heat shock proteins (HSP) protects isolated islet cells against the cytotoxicity of inflammatory mediators in vitro. Very little information is available about the effect of HSP overexpression on function of preconditioned islet grafts. The present study investigated the function of heat-exposed pig islets after transplantation into immunocompetent mice in comparison with in vitro resistance against inflammatory mediators. Pig islets were preconditioned at 43°C or sham treated prior to subcapsular transplantation into diabetic C57/Bl6j mice. Nondiabetic mice simultaneously receiving preconditioned and control islets were subjected to bilateral nephrectomy for determination of pig insulin. Resistance against H 2 O 2 , NO, human Il-1β, IFN-γ, or TNF-α was assessed by trypan blue exclusion and insulin determination. Heat-induced protein expression was confirmed by Western blot analysis. Graft preconditioning increased resistance against H 2 O 2 , NO, or cytokines (p < 0.05) but decreased survival in nondiabetic mice (p < 0.05) and function in diabetic mice (p < 0.01). Upregulation of caspase-3 activity as well as Bax, Fas, FasL, and DFF expression (p < 0.05) indicated simultaneous induction of apoptosis. The coexpression of HSP and proapoptotic proteins reveals the dual character of the stress response simultaneously starting mechanisms for protection and apoptosis. In vitro assays seem to reflect only insufficiently the situation of islets after transplantation.https://doi.org/10.3727/000000003771000200 |
| spellingShingle | Daniel Brandhorst Ph.D. Heide Brandhorst Vidya Kumarasamy Adel Maataoui Alexandra Alt Mathias D. Brendel Reinhard G. Bretzel Hyperthermic Preconditioning Protects Pig Islet Grafts from Early Inflammation but Enhances Rejection in Immunocompetent Mice Cell Transplantation |
| title | Hyperthermic Preconditioning Protects Pig Islet Grafts from Early Inflammation but Enhances Rejection in Immunocompetent Mice |
| title_full | Hyperthermic Preconditioning Protects Pig Islet Grafts from Early Inflammation but Enhances Rejection in Immunocompetent Mice |
| title_fullStr | Hyperthermic Preconditioning Protects Pig Islet Grafts from Early Inflammation but Enhances Rejection in Immunocompetent Mice |
| title_full_unstemmed | Hyperthermic Preconditioning Protects Pig Islet Grafts from Early Inflammation but Enhances Rejection in Immunocompetent Mice |
| title_short | Hyperthermic Preconditioning Protects Pig Islet Grafts from Early Inflammation but Enhances Rejection in Immunocompetent Mice |
| title_sort | hyperthermic preconditioning protects pig islet grafts from early inflammation but enhances rejection in immunocompetent mice |
| url | https://doi.org/10.3727/000000003771000200 |
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