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核糖体蛋白S19二聚体和C5a受体在吞噬性白细胞病理生理功能中的作用。

Roles of the ribosomal protein S19 dimer and the C5a receptor in pathophysiological functions of phagocytic leukocytes.

作者信息

Yamamoto Tetsuro

机构信息

Department of Molecular Pathology, Faculty of Medical and Pharmaceutical Sciences, Kumamoto University Graduate School, Honjo, Kumamoto, Japan.

出版信息

Pathol Int. 2007 Jan;57(1):1-11. doi: 10.1111/j.1440-1827.2007.02049.x.

DOI:10.1111/j.1440-1827.2007.02049.x
PMID:17199736
Abstract

Monocytes and neutrophils, the major phagocytic leukocytes, migrate to inflammatory sites by sensing chemoattractants such as anaphylatoxin C5a with membrane receptors such as C5a receptor. Upon stimulation, the leukocytes increase cytoplasmic Ca(2+) concentration and generate radical oxygen species. These leukocytes have different functions in inflammation. Neutrophils migrate more rapidly and induce vascular plasma leakage upon infiltration. Monocytes infiltrate tissue more slowly but have superior capacities of phagocytosis and antigen presentation. There must be mechanisms to separately recruit the leukocyte species at an inflammatory site. Ribosomal protein S19 (RP S19) is a component of ribosome. During apoptosis, RP S19 is dimerized and obtains a ligand capacity to C5a receptor. The RP S19 dimer attracts monocytes to phagocytically clear the apoptotic cells that released the dimer molecules. The phagocytic monocytes/macrophages then translocate to regional lymph nodes and present apoptotic cell-derived antigens. Oppositely, the RP S19 dimer inhibits C5a-induced neutrophil migration and promotes apoptosis of neutrophils via the C5a receptor. The RP S19 dimer seems to prevent excessive tissue destruction induced by neutrophils. Skp is a molecular chaperon of Gram-negative bacteria. Skp also attracts monocytes and neutrophils as a ligand of C5a receptor. However, it promotes neither cytoplasmic Ca(2+) enhancement nor radical oxygen generation.

摘要

单核细胞和中性粒细胞是主要的吞噬性白细胞,它们通过膜受体(如C5a受体)感知趋化因子(如过敏毒素C5a),迁移至炎症部位。受到刺激后,白细胞会增加细胞质中钙离子的浓度并产生活性氧。这些白细胞在炎症中具有不同的功能。中性粒细胞迁移速度更快,浸润时会诱导血管血浆渗漏。单核细胞浸润组织的速度较慢,但具有更强的吞噬作用和抗原呈递能力。在炎症部位,必然存在分别招募这两种白细胞的机制。核糖体蛋白S19(RP S19)是核糖体的一个组成部分。在细胞凋亡过程中,RP S19会二聚化,并获得与C5a受体结合的配体能力。RP S19二聚体吸引单核细胞吞噬清除释放出二聚体分子的凋亡细胞。吞噬后的单核细胞/巨噬细胞随后转移至局部淋巴结并呈递凋亡细胞衍生的抗原。相反,RP S19二聚体通过C5a受体抑制C5a诱导的中性粒细胞迁移,并促进中性粒细胞凋亡。RP S19二聚体似乎能防止中性粒细胞诱导的过度组织破坏。Skp是革兰氏阴性菌的一种分子伴侣。Skp作为C5a受体的配体,也能吸引单核细胞和中性粒细胞。然而,它既不促进细胞质钙离子浓度升高,也不促进活性氧的产生。

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