ROLE OF LYMPHOCYTES AND MACROPHAGES IN BONE REMODELING

淋巴细胞和巨噬细胞在骨重塑中的作用

• 批准号: 3151962
• 负责人: ROLAND E BARON
• 金额: $ 14.54万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1981
• 资助国家: 美国
• 起止时间: 1981-09-01 至 1987-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3151962
• 关键词: B lymphocyte; T lymphocyte; bone neoplasms; histochemistry /cytochemistry; homeostasis; lymphocyte; lymphokines; macrophage; metastasis; orphan disease /drug; osteopetrosis; osteoporosis; periodontium disorder; phagocytes; physiologic bone resorption; reticuloendothelial system; skeletal disorder

The long term goal of this proposal is to elucidate the role of the immune system in the regulation of bone remodeling, under both normal and pathological conditions. Two approaches are described to investigate possible interactions between the cells of the immune system and the cells of the skeletal system as well as soluble products of these cells as potential agents and effectors of these interactions. The first approach concerns the lymphokine osteoclast activating factor (OAF). The cellular interactions leading to the secretion of this product will be further studied by the use of specific monoclonal antibodies to cell surface antigens. In parallel, purification of this lymphokine will be attempted, possibly using T-cell hybrids as a source, by conventional purification methods and also by inhibition assays, affinity chromatography and immune overlay of electrophhoretical transfers if an antibody to this protein can be raised. The second approach deals with studies in vivo on immunodeficient animals (Nudes, Motheaten, Beige) on normal animals on which specific immune defects are induced and on mutants with skeletal defects (osteopetrotic). Parallel studies will be made on bone remodeling and immune functions in these three groups of animals. Finally, immunohistochemical localization of cells of the immune system relative to bone cells will be made as well as attempts at localizing known surface antigens on bone cells. In the long run, these studies may be critical importance in the understanding of the regulation of skeletal diseases such as periodontal disease, osteopetrosis and osteoporosis and primary and metastatic bone tumors. They may also lead to an expanded concept of the role of the immune system in homeostasis.

该提议的长期目标是阐明免疫的作用 在正常和 病理状况。 描述了两种方法以调查 免疫系统和细胞细胞之间的可能相互作用 这些细胞的骨骼系统以及这些细胞的可溶产品 这些相互作用的潜在代理和效应因素。 第一种方法 涉及淋巴细胞破骨细胞激活因子（OAF）。 细胞 导致该产品分泌的互动将进一步 通过使用特定的单克隆抗体对细胞表面进行研究 抗原。 同时，将尝试纯化该淋巴因子， 可能通过常规纯化使用T细胞杂种作为来源 方法以及通过抑制测定，亲和力色谱和免疫 如果对该蛋白的抗体可以 长大。 第二种方法涉及体内研究 免疫缺陷的动物（裸动物，motheaten，米色）在正常动物上 哪些特异性免疫缺陷是诱导的，并在具有骨骼的突变体上 缺陷（骨质原子质）。 将对骨骼重塑进行平行研究 这三组动物中的免疫功能。 最后， 免疫组织的免疫组织化学定位相对于 将制作骨细胞，并尝试定位已知表面 骨细胞上的抗原。 从长远来看，这些研究可能至关重要 在理解骨骼疾病的调节中的重要性 作为牙周疾病，骨质疏松症和骨质疏松症以及原发性疾病 转移性骨肿瘤。 它们也可能导致扩展的概念 免疫系统在体内平衡中的作用。

项目成果

Thymus-derived lymphocytes and their interactions with macrophages are required for the production of osteoclast-activating factor in the mouse.

胸腺来源的淋巴细胞及其与巨噬细胞的相互作用是小鼠破骨细胞激活因子产生所必需的。

• DOI: 10.1073/pnas.81.7.2181
• 发表时间: 1984
• 期刊: Proceedings of the National Academy of Sciences of the United States of America
• 影响因子: 11.1
• 作者: Horowitz,M;Vignery,A;Gershon,RK;Baron,R
• 通讯作者: Baron,R

Squamous carcinoma model of humoral hypercalcemia of malignancy.

恶性肿瘤体液高钙血症的鳞状细胞癌模型。

• DOI: 10.1210/endo-115-6-2384
• 发表时间: 1984
• 期刊: Endocrinology
• 影响因子: 4.8
• 作者: Gkonos,PJ;Hayes,T;Burtis,W;Jacoby,R;McGuire,J;Baron,R;Stewart,AF
• 通讯作者: Stewart,AF