人源抗ICAM-1单链抗体的制备及其生物学活性研究
发布时间：2019-04-18 17:52
【摘要】： 细胞间黏附分子-1(ICAM-1)作为淋巴细胞功能相关抗原-1 (LFA-1)的配体可介导白细胞与血管内皮细胞的黏附及白细胞穿出血管壁,同时促使更多中性粒细胞和嗜酸性粒细胞转移至炎症区,释放更多的氧化自由基、蛋白酶和花生四烯酸等代谢产物,加重组织损伤程度,进而造成病理损伤,在炎症性疾病的发生与发展过程中发挥重要作用,ICAM-1成为炎症相关性疾病治疗新的靶点。 本研究旨在利用噬菌体展示技术应用Tomlinson I+J噬菌体抗体库制备人源抗ICAM-1单链抗体,并对工程菌进行表达条件优化、目的蛋白纯化工艺研究及生物学活性研究。人血管内皮细胞-单核细胞黏附抑制实验表明,制备的人源抗ICAM-1单链抗体能够有效抑制血管内皮细胞与单核细胞之间的黏附,对炎症性病理反应有较强的抑制作用,本课题研究为临床炎症相关性疾病的初步治疗奠定基础。
[Abstract]:Intercellular adhesion molecule-1 (ICAM-1), as a ligand of lymphocyte function-related antigen-1 (LFA-1), mediates leukocyte adhesion to vascular endothelial cells and leukocytes through the vascular wall. At the same time, it causes more neutrophils and eosinophils to transfer to the inflammatory zone and releases more metabolites such as oxidative free radicals, protease and arachidonic acid, which aggravates the degree of tissue damage and then causes pathological damage. ICAM-1 plays an important role in the occurrence and development of inflammatory diseases, and it has become a new target for the treatment of inflammatory-related diseases. The aim of this study was to prepare human anti-ICAM-1 scFv by phage display technique using Tomlinson I J phage antibody library, and to optimize the expression conditions of the recombinant strain, and to study the purification technology and biological activity of the protein. Human vascular endothelial cell-monocyte adhesion inhibition test showed that the prepared human anti-ICAM-1 single chain antibody could effectively inhibit the adhesion between vascular endothelial cells and monocytes, and had a strong inhibitory effect on inflammatory pathological response. This study lays a foundation for the preliminary treatment of clinical inflammation-related diseases.
【学位授予单位】：吉林大学
【学位级别】：硕士
【学位授予年份】：2009
【分类号】：R392.12
[Abstract]:Intercellular adhesion molecule-1 (ICAM-1), as a ligand of lymphocyte function-related antigen-1 (LFA-1), mediates leukocyte adhesion to vascular endothelial cells and leukocytes through the vascular wall. At the same time, it causes more neutrophils and eosinophils to transfer to the inflammatory zone and releases more metabolites such as oxidative free radicals, protease and arachidonic acid, which aggravates the degree of tissue damage and then causes pathological damage. ICAM-1 plays an important role in the occurrence and development of inflammatory diseases, and it has become a new target for the treatment of inflammatory-related diseases. The aim of this study was to prepare human anti-ICAM-1 scFv by phage display technique using Tomlinson I J phage antibody library, and to optimize the expression conditions of the recombinant strain, and to study the purification technology and biological activity of the protein. Human vascular endothelial cell-monocyte adhesion inhibition test showed that the prepared human anti-ICAM-1 single chain antibody could effectively inhibit the adhesion between vascular endothelial cells and monocytes, and had a strong inhibitory effect on inflammatory pathological response. This study lays a foundation for the preliminary treatment of clinical inflammation-related diseases.
【学位授予单位】：吉林大学
【学位级别】：硕士
【学位授予年份】：2009
【分类号】：R392.12
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