Molecular mechanisms of the carbohydrate-dependent recognition and clearance of apoptotic cells and oxidized cells by macrophages.

研究了碳水化合物介导的巨噬细胞识别凋亡细胞和氧化细胞的分子机制。主要发现如下：1.在凋亡的T淋巴细胞的细胞膜上，CD 43瞬时形成帽，2.磷脂酰丝氨酸（PS）暴露和暴露的PS介导的巨噬细胞对凋亡细胞的识别晚于CD 43加帽阶段。在细胞系和原代细胞系统中均观察到早期凋亡细胞的巨噬细胞介导的识别。4.由于诱导CD 43加帽而不凋亡也导致碳水化合物介导的识别，CD 43加帽是细胞凋亡的关键事件。氧化和凋亡细胞介导的识别似乎受到细胞内氧化还原系统和钙信号的调节。6.通过以下工作鉴定了用于碳水化合物介导的氧化细胞和凋亡细胞识别的巨噬细胞受体是已知的蛋白质p110：1）p110表达于巨噬细胞表面; 2）抗p110抗体可抑制凋亡细胞与巨噬细胞的结合;可溶性p110重组蛋白可抑制凋亡细胞与巨噬细胞的结合，寡糖可阻断其抑制活性。4）表达p110重组蛋白的非吞噬细胞能识别早期凋亡细胞，而野生型细胞不能。

Molecular mechanisms of the carbohydrate-mediated recognition of apoptotic cells and oxidized cells by macrophages were investigated. The major findings are listed below.1.On the cell membrane of T-lymphocytes undergoing apoptosis, CD43 transiently forms caps, and the cells become susceptible to macrophage recognition through the carbohydrate chains of the CD43 caps.2.Phosphatidylserine (PS) exposure and the exposed PS-mediated macrophage recognition of the apoptotic cells were observed later than the CD43 capping stage.3.The carbohydrate-mediated macrophage recognition of the early apoptotic cells were observed in both cell line and primary cell systems.4.Because induction of CD43 capping without apoptosis resulted also in the carbohydrate-mediated recognition, CD43 capping was a critical event for the recognition.5.The activity of the macrophage receptor for the carbohydrate-mediated recognition of oxidized and apoptotic cells appeared to be regulated by intracellular redox system and calcium signaling.6.The macrophage receptor for the carbohydrate-mediated recognition of oxidized cells and apoptotic cells was identified to be a known protein p110 by the following works :1)p110 was demonstrated to be expressed on the macrophage surface.2)Anti p110 antibody inhibited the binding of apoptotic cells and macrophages.3)A soluble recombinant protein of p110 inhibited the binding of apoptotic cells and macrophages, and oligosaccharides blocked its inhibitory activity.4) Non-phagocytic cells expressing recombinant p110 on cell surface were able to recognize the early apoptotic cells, while the wild type cells were not.