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Mac-1的结构与功能及其在肿瘤免疫治疗中的作用
  • ISSN号:1007-3639
  • 期刊名称:《中国癌症杂志》
  • 时间:0
  • 分类:R730.51[医药卫生—肿瘤;医药卫生—临床医学]
  • 作者机构:[1]第二军医大学病理生理教研室,上海200433, [2]第二军医大学生理教研室,上海200433
  • 相关基金:国家自然科学基金面上项目(30270522)资助.
中文摘要:

Mac-1是位于白细胞表面参于机体防御作用及免疫反应的重要的粘附分子,它由α(CD11b)和β(CD18)两个亚基以非共价键的方式缔合成异二聚体,Mac-1的分子结构中有两个重要的区域:一个是识别蛋白配体的1-域,另一个是识别多糖的凝集素部位。Mac-1在几乎所有中性粒细胞、单核细胞、嗜酸件细胞和NK细胞上广泛表达,巨噬细胞、B细胞和T细胞表达较少。Mac-1具有两种主要的功能:一是与活化的内皮细胞表面上的ICAM-1高亲和力的粘附,介导白细胞的游走与渗出。二是作为iC3b的受体,介导白细胞对iC3b调理的微生物或靶细胞的细胞毒功能。此外,Mac-1还能与许多细胞膜表面的糖蛋白缔合成复合物,介导信号的跨膜转导。研究发现,可溶性的β-葡聚糖能够结合并致敏Mac-1继而触发吞噬细胞或NK细胞对iC3b-调理的肿瘤细胞的细胞毒反应,这一发现为β-葡聚糖在肿瘤免疫治疗中的应用提供了理论基础。大多数的人类或动物的肿瘤细胞能活化补体并在原位被iC3b调理,肿瘤细胞表面的iC3b结合到β-葡聚糖致敏了的Mac-1后,吞噬细胞或NK细胞就能杀伤肿瘤细胞。

英文摘要:

Mac-1, an adhesion molecule expressed on the surface of leukocytes, plays an important role in host-defence function and immunological response. It consists of two noncovalently linked polypeptides known as α( CD111b) and β(CD18) subunits. It contains two important domains known as l-domain which recognizes protein ligands and the lectin domain which recognizes polysaccharides. Mac-1 is expressed on nearly all neutrophils, monocytes, eosinophils and NK cells, but less on B cells, T cells and macrophages. Mac-1 functions as both an adhesion molecule for ICAM-1 expressed by stimulated endothelium mediating the diapedesis of leukocytes across the endothelium and a receptor for the iC3b fragment of complement responsible for cytotoxicity to microorganisms or target ceils opsonized with iC3b. It can also form a complex with many membrane glycoproteins, functioning as a signal transducing partner for them. An important finding was that soluble β-glucan could bind to Mac-1 and prime the receptor for cytotoxic function in response to iC3b-opsonized tumors, thus may pave the way for development of β-gh.can-like drugs that could generate Mac-1-dependent cytotoxicity following a humoral response to tumor antigens elicited by vaccines that would cause tumors to be opsonized with Abs and iC3b in cancer immunotherapy.

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期刊信息
  • 《中国癌症杂志》
  • 中国科技核心期刊
  • 主管单位:中华人民共和国教育部
  • 主办单位:复旦大学附属肿瘤医院
  • 主编:沈镇宙
  • 地址:上海市徐汇区东安路270号6号楼3楼
  • 邮编:200032
  • 邮箱:zgazzz@163.com
  • 电话:021-64188274 64175590-3574
  • 国际标准刊号:ISSN:1007-3639
  • 国内统一刊号:ISSN:31-1727/R
  • 邮发代号:4-575
  • 获奖情况:
  • 国内外数据库收录:
  • 被引量:19590