Ma J, Chen T, Mandelin J, Ceponis A, Miller N E, Hukkanen M, Ma G F, Konttinen Y T
Department of Anatomy, Institute of Biomedicine, University of Helsinki, Helsinki, Finland.
Cell Mol Life Sci. 2003 Nov;60(11):2334-46. doi: 10.1007/s00018-003-3020-0.
IFN-gamma rapidly primes the macrophage via JAK1/2-STAT1 pathway so that it can subsequently undergo a slower classical type 1 activation upon exposure to T helper (Th)1 cytokines such as IFNgamma or other activators, including tumor necrosis factor and lipopolysaccharide, e.g. in intracellular killing of phagocytosed Mycobacterium tuberculosis. If instead it is driven by Th2 cytokines interleukin (IL)-4 and IL-13, it undergoes alternate type 2 activation, which enhances endocytotic antigen uptake and presentation, mast cell and eosinophil involvement and type 2 granuloma formation, e.g. in response to parasitic and extracellular pathogens. Particle-induced macrophage activation was shown to differ from classical and alternate activation, showing in DNA microarray experiments (complete linkage/ Euclidean distance metric analysis) upregulation of nonsecreted structural/signaling molecules and lack of secreted proinflammatory cyto- and chemokines. The switch-off (deactivation) of already activated macrophages is an active, controlled process in which IL-10 and corticosteroids play important roles and to which 15dPGJ2, PGA1/2 and vasoactive intestinal peptide often contribute.
γ干扰素通过JAK1/2-STAT1途径迅速使巨噬细胞致敏，以便其随后在暴露于T辅助（Th）1细胞因子（如γ干扰素）或其他激活剂（包括肿瘤坏死因子和脂多糖）时，能够经历较慢的经典1型激活，例如在细胞内杀死吞噬的结核分枝杆菌时。相反，如果它由Th2细胞因子白细胞介素（IL）-4和IL-13驱动，它会经历交替的2型激活，这会增强内吞性抗原摄取和呈递、肥大细胞和嗜酸性粒细胞参与以及2型肉芽肿形成，例如对寄生虫和细胞外病原体的反应。颗粒诱导的巨噬细胞激活显示不同于经典激活和交替激活，在DNA微阵列实验（完全连锁/欧几里得距离度量分析）中显示非分泌性结构/信号分子上调，且缺乏分泌性促炎细胞因子和趋化因子。已激活巨噬细胞的关闭（失活）是一个活跃的、受控制的过程，其中IL-10和皮质类固醇起重要作用，15dPGJ2、PGA1/2和血管活性肠肽也常常参与其中。
