Goulding N J, Euzger H S, Butt S K, Perretti M
Arthritis Research Section, St. Bartholomew's & Royal London School of Medicine & Dentistry, UK.
Inflamm Res. 1998 Oct;47 Suppl 3:S158-65. doi: 10.1007/s000110050310.
Neutrophils have been implicated in mediating much of the tissue damage associated with chronic inflammatory diseases such as rheumatoid arthritis, where they are involved in destruction of both cartilage and bone. Glucocorticoids are powerful anti-inflammatory agents, often used in the treatment of this autoimmune disease. They exert significant inhibitory effects on neutrophil activation and functions, such as chemotaxis, adhesion, transmigration, apoptosis, oxidative burst, and phagocytosis. The mechanisms by which glucocorticoids exert these effects on neutrophils are unclear. Evidence from studies of inflammation in human subjects and animal models suggests that annexin-I an endogenous, glucocorticoid-induced protein also known as lipocortin-1, has a pivotal role in modulating neutrophil activation, transmigratory, and phagocytic functions. Furthermore, we present evidence for altered neutrophil functions in rheumatoid arthritis that correspond to a significantly reduced capacity of these cells to bind annexin-I. A proposed novel pathway for glucocorticoid actions on neutrophils involving annexin-I could explain the development of chronic neutrophil activation in diseases such as rheumatoid arthritis.
中性粒细胞被认为在介导与慢性炎症性疾病（如类风湿性关节炎）相关的许多组织损伤中起作用，在类风湿性关节炎中，中性粒细胞参与软骨和骨的破坏。糖皮质激素是强大的抗炎剂，常用于治疗这种自身免疫性疾病。它们对中性粒细胞的激活和功能，如趋化性、黏附、迁移、凋亡、氧化爆发和吞噬作用，具有显著的抑制作用。糖皮质激素对中性粒细胞发挥这些作用的机制尚不清楚。来自人体受试者和动物模型炎症研究的证据表明，膜联蛋白-I（一种内源性的、糖皮质激素诱导的蛋白质，也称为脂皮质蛋白-1）在调节中性粒细胞的激活、迁移和吞噬功能中起关键作用。此外，我们提供了类风湿性关节炎中中性粒细胞功能改变的证据，这些改变对应于这些细胞结合膜联蛋白-I的能力显著降低。一种提出的涉及膜联蛋白-I的糖皮质激素作用于中性粒细胞的新途径，可以解释类风湿性关节炎等疾病中慢性中性粒细胞激活的发展。
