2002 Fiscal Year Final Research Report Summary
An experimental study to detect unknown or unexpected genes expressed in the developmental phase of transplant vasculopathy.
| Project/Area Number |
13671385
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Thoracic surgery
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| Research Institution | Osaka University |
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Principal Investigator |
SAKAKIDA Satoru Osaka University Graduate School of Medicine ・ Associate Professor, 医学系研究科, 助教授 (90311753)
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| Co-Investigator(Kenkyū-buntansha) |
FUKUSHIMA Norihide Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (30263247)
SAWA Yoshiki Osaka University Graduate School of Medicine, Associate Professor, 医学系研究科, 講師 (00243220)
SHIRAKURA Ryota Osaka University Graduate School of Medicine, Professor, 医学系研究科, 教授 (00116047)
MATSUMIYA Goro Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (20314312)
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| Project Period (FY) |
2001 – 2002
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| Keywords | Chronic rejection / heterotopic rat heart transplantation / Retransplantation / quantitative RT-PCR / mRNA differential display / B cells / Antibody / RFDD |
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| Research Abstract |
Molecular mechanism of pathological neointima-progression was experimentally investigated in rat model of transplant vasculopathy. In the model, heart was first grafted into an allogeneic host and retransplanted to (donor x host) F1 or nude rat before morphologically apparent vascular change was detected. Thereby, the vascular lesion in the model was progressed under the condition in which allogeneic immune responses were terminated. Genes preferentially expressed in the grafts progressing the vascular lesion were searched by two methods of mRNA differential display; PCR-based differential display (PCR-DD) and restriction fragment differential display (RFDD). Immunoglobulin kappa chain (Igk), MHC class II gene, and CD11b genes was detected by either of the methods. Interestingly, expressions of Igk and MHC class II genes were minimally detected at the time of retransplantation but they peaked at the time of neointimal progression, whereas expressions of allogeneic T-cell-related genes peaked just after the retransplantation and rapidly decreased thereafter. Immunohistochemical staining showed that infiltrated B-cells were specifically found in pathological neointima but not in myocardium or interstitium of the same grafts. Expression patterns of B-lymphocyte chemoattractant, its receptor CXCR5, CD40 ligand, and B7.2 genes suggested the B cells were actively recreited to the grafts after retransplantation and stimulated in the lesion. In fact, specific depositions of IgG and IgM antibodies on the progressing neointima were detected long after the retransplantation but not in the onset of neointimal formation.
Collectively, we propose that formation of non-allogeneic antibody inside the lesion, which specifically binds to the pathological neointima but not to the normal intima, may have a role in the progression of transplant vasculopathy.
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