Yona Simon, Heinsbroek Sigrid E M, Peiser Leanne, Gordon Siamon, Perretti Mauro, Flower Roderick J
Department of Biochemical Pharmacology, The William Harvey Research Institute, St Bartholomew's and the Royal London School of Medicine, University of London.
Br J Pharmacol. 2006 Jun;148(4):469-77. doi: 10.1038/sj.bjp.0706730. Epub 2006 Apr 24.
The role of the anti-inflammatory protein annexin-A1 (Anx-A1) in the phagocytic process has been investigated using a murine bone marrow culture-derived macrophage model from Anx-A1(+/+) and Anx-A1(-/-) mice. Macrophages prepared from Anx-A1(-/-) mice exhibited a reduced ingestion of zymosan, Neisseria meningitidis or sheep red blood cells, when compared to Anx-A1(+/+) cells and in the case of zymosan this effect was also mirrored by a reduced clearance in vivo when particles were injected into the peritoneal cavity of Anx-A1(-/-) mice. The ablation of the Anx-A1 gene did not cause any apparent cytoskeletal defects associated with particle ingestion but the cell surface expression of the key adhesion molecule CD11b was depressed in the Anx-A1(-/-) cells providing a possible explanation for the attenuated phagocytic potential of these cells. The production of the cytokines TNFalpha and IL-6 was increased in Anx-A1(-/-) macrophages following phagocytosis of all types of particle.
利用来自野生型(Anx-A1(+/+))和Anx-A1基因敲除型(Anx-A1(-/-))小鼠的骨髓培养来源的巨噬细胞模型,研究了抗炎蛋白膜联蛋白A1(Anx-A1)在吞噬过程中的作用。与Anx-A1(+/+)细胞相比,Anx-A1(-/-)小鼠制备的巨噬细胞对酵母聚糖、脑膜炎奈瑟菌或绵羊红细胞的摄取减少,在酵母聚糖的情况下,当将颗粒注射到Anx-A1(-/-)小鼠的腹腔中时,体内清除率降低也反映了这种作用。Anx-A1基因的缺失并未导致与颗粒摄取相关的任何明显细胞骨架缺陷,但关键黏附分子CD11b在Anx-A1(-/-)细胞中的细胞表面表达降低,这为这些细胞吞噬潜力减弱提供了一个可能的解释。在吞噬所有类型颗粒后,Anx-A1(-/-)巨噬细胞中细胞因子TNFα和IL-6的产生增加。