Dale David C, Boxer Laurence, Liles W Conrad
Department of Medicine, University of Washington School of Medicine, Seattle A98195, USA.
Blood. 2008 Aug 15;112(4):935-45. doi: 10.1182/blood-2007-12-077917.
The production and deployment of phagocytes are central functions of the hematopoietic system. In the 1950s, radioisotopic studies demonstrated the high production rate and short lifespan of neutrophils and allowed researchers to follow the monocytes as they moved from the marrow through the blood to become tissue macrophages, histiocytes, and dendritic cells. Subsequently, the discovery of the colony-stimulating factors greatly improved understanding the regulation of phagocyte production. The discovery of the microbicidal myeloperoxidase-H2O2-halide system and the importance of NADPH oxidase to the generation of H2O2 also stimulated intense interest in phagocyte disorders. More recent research has focused on membrane receptors and the dynamics of the responses of phagocytes to external factors including immunoglobulins, complement proteins, cytokines, chemokines, integrins, and selectins. Phagocytes express toll-like receptors that aid in the clearance of a wide range of microbial pathogens and their products. Phagocytes are also important sources of pro- and anti-inflammatory cytokines, thus participating in host defenses through a variety of mechanisms. Over the last 50 years, many genetic and molecular disorders of phagocytes have been identified, leading to improved diagnosis and treatment of conditions which predispose patients to the risk of recurrent fevers and infectious diseases.
吞噬细胞的产生和部署是造血系统的核心功能。20世纪50年代,放射性同位素研究证明了中性粒细胞的高产生率和短寿命,并使研究人员能够追踪单核细胞从骨髓经血液迁移至组织巨噬细胞、组织细胞和树突状细胞的过程。随后,集落刺激因子的发现极大地增进了对吞噬细胞产生调节的理解。杀菌性髓过氧化物酶-H2O2-卤化物系统的发现以及NADPH氧化酶对H2O2生成的重要性也激发了人们对吞噬细胞疾病的浓厚兴趣。最近的研究集中在膜受体以及吞噬细胞对包括免疫球蛋白、补体蛋白、细胞因子、趋化因子、整合素和选择素在内的外部因素的反应动力学上。吞噬细胞表达Toll样受体,有助于清除多种微生物病原体及其产物。吞噬细胞也是促炎和抗炎细胞因子的重要来源,因此通过多种机制参与宿主防御。在过去50年里,已经发现了许多吞噬细胞的遗传和分子疾病,从而改善了对使患者易患反复发热和传染病风险的病症的诊断和治疗。