Leverrier Y, Lorenzi R, Blundell M P, Brickell P, Kinnon C, Ridley A J, Thrasher A J
Ludwig Institute for Cancer Research, Royal Free and University College Medical School Branch, London, United Kingdom.
J Immunol. 2001 Apr 15;166(8):4831-4. doi: 10.4049/jimmunol.166.8.4831.
Phagocytosis of apoptotic cells by macrophages and dendritic cells is necessary for clearance of proinflammatory debris and for presentation of viral, tumor, and self Ags. While a number of receptors involved in the cognate recognition of apoptotic cells by phagocytes have been identified, the signaling events that result in internalization remain poorly understood. Here we demonstrate that clearance of apoptotic cells is accompanied by recruitment of the Wiskott-Aldrich syndrome (WAS) protein to the phagocytic cup and that it's absence results in delayed phagocytosis both in vitro and in vivo. Therefore, we propose that WAS protein plays an important and nonredundant role in the safe removal of apoptotic cells and that deficiency contributes significantly to the immune dysregulation of WAS. The efficiency of apoptotic cell clearance may be a key determinant in the suppression of tissue inflammation and prevention of autoimmunity.
巨噬细胞和树突状细胞对凋亡细胞的吞噬作用对于清除促炎碎片以及呈递病毒、肿瘤和自身抗原而言是必要的。虽然已经鉴定出许多参与吞噬细胞对凋亡细胞进行同源识别的受体,但导致内化的信号转导事件仍知之甚少。在此,我们证明凋亡细胞的清除伴随着威斯科特-奥尔德里奇综合征(WAS)蛋白募集到吞噬杯,并且其缺失导致体外和体内吞噬作用延迟。因此,我们提出WAS蛋白在安全清除凋亡细胞中发挥重要且非冗余的作用,并且其缺陷对WAS的免疫失调有显著影响。凋亡细胞清除的效率可能是抑制组织炎症和预防自身免疫的关键决定因素。