ROLE OF CALCITONIN GENE RELATED PEPTIDE IN ALLOGRAFTS

降钙素基因相关肽在同种异体移植物中的作用

• 批准号: 3425931
• 负责人: Agnes Vignery
• 金额: $ 4.2万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-03-01 至 1995-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3425931
• 关键词: bone transplantation; calcitonin gene related peptide; heart transplantation; histology; homologous transplantation; immunization; immunocytochemistry; immunosuppressive; laboratory mouse; laboratory rat; microscopy; nerve endings; neurofilament; neuroimmunomodulation; nonhuman therapy evaluation; osteocytes; skin transplantation; transplant rejection

Mounting evidence from the literature indicates that the immune system and bone cells closely interact both directly and indirectly via cytokines and soluble factors. Most recently, we have generated evidence that some immune cells express functional receptors for the neuropeptide calcitonin gene related peptide (CGRP). We have shown that CGRP in a potent immunosuppressive peptide by virtue of inhibiting T lymphocytes to produce interleukin 2 as well as cytokines which promote osteoclast differentiation and activation. Since CGRP directly inhibits osteoclast activity via calcitonin receptors, and stimulates osteogenesis in vitro, we hypothesize that CGRP plays a central role in bone homeostasis and is a potential candidate to optimize the acceptance of bone allografts. The specific aims of this proposal are: 1. To define the distribution of CGRP positive nerve endings in bone and bone marrow in vivo by immunolocalization; compare it to that observed during bone growth and repair, as well as in bone transplant and implant model systems. 2. To investigate the immunosuppressive role of CGRP in vivo using allografts. The long term goal of this research is to develop new therapies that have the potential to improve the survival of transplanted calcified tissues.

越来越多的文献证据表明，免疫系统 和骨细胞直接或间接地通过 细胞因子和可溶性因子。 最近，我们有证据表明 一些免疫细胞表达神经肽的功能性受体 降钙素基因相关肽（CGRP）。 我们已经证明，CGRP在一个 通过抑制T淋巴细胞的有效免疫抑制肽 产生白细胞介素2以及促进破骨细胞的细胞因子 分化和激活。 由于CGRP直接抑制破骨细胞 活性通过降钙素受体，并刺激体外骨生成， 我们假设CGRP在骨稳态中起着中心作用， 优化骨同种异体移植物接受性的潜在候选者。 这项建议的具体目标是： 1.目的：明确CGRP阳性神经末梢在骨组织中的分布， 通过免疫定位在体内骨髓中;将其与观察到的进行比较 在骨生长和修复期间，以及在骨移植和植入中， 模型系统 2.为了研究CGRP在体内的免疫抑制作用， 同种异体移植 这项研究的长期目标是开发新的治疗方法， 提高移植钙化组织存活率的潜力。