Fas (CD95) induces proinflammatory cytokine responses by human monocytes and monocyte-derived macrophages
Fas (CD95) induces proinflammatory cytokine responses by human monocytes and monocyte-derived macrophages
复制标题
DOI：
10.4049/jimmunol.170.12.6209
复制
发表时间：
2003-06-15
影响因子：
4.4
通讯作者：
Liles, WC
中科院分区：
文献类型：
--
作者：
Park, DR;Thomsen, AR;Liles, WC
Fas（CD 95，APO-1）被认为是TNFR超家族的原型细胞死亡受体。Fas诱导的细胞凋亡通常被认为是一个非炎症过程，有助于免疫和炎症反应的沉默解决。然而，越来越多的证据表明Fas也可以诱导细胞活化信号。我们假设Fas可以激活。正常人单核细胞和巨噬细胞的促炎细胞因子应答。通过阴性免疫选择从来自健康志愿者的静脉血的PBMC部分分离单核细胞，并在体外培养单核细胞衍生的巨噬细胞。单核细胞和单核细胞衍生的巨噬细胞在Fas连接后释放TNF-α和IL-8，并且来自Fas活化的单核细胞和巨噬细胞的条件培养基诱导中性粒细胞定向迁移。趋化性测定。Fas诱导的单核细胞细胞因子反应与单核细胞凋亡、NF-κ B核转位和细胞因子基因表达相关，并可被caspase抑制剂阻断，但不被IL-1 β信号抑制剂阻断。相反，Fas诱导的巨噬细胞细胞因子反应发生在细胞凋亡的情况下，caspase独立，表明成熟依赖性差异的Fas信号通路，导致促炎细胞因子的诱导。循环单核细胞和组织巨噬细胞上的Fas连接可能诱导促炎细胞因子反应，而不是有助于炎症的消退，所述促炎细胞因子反应可以引发急性炎症反应和组织损伤。
Fas (CD95, APO-1) is regarded as the prototypical cell death receptor of the TNFR superfamily. Fas-induced apoptosis is generally considered to be a noninflammatory process, contributing to the silent resolution of immune and inflammatory responses. However, accumulating evidence indicates that Fas may also induce cellular activation signals'. We hypothesized that Fas could activate. proinflammatory cytokine responses by normal human monocytes and macrophages. Monocytes were isolated by negative immunoselection from the PBMC fraction of venous blood from healthy volunteers, and monocyte-derived macrophages were cultivated in vitro. Both monocytes and monocyte-derived macrophages released TNF-alpha and IL-8 following Fas ligation, and conditioned medium from Fas-activated monocytes and macrophages induced the directed migration of neutrophils in. a chemotaxis assay. Fas-induced monocyte cytokine responses were associated with monocyte apoptosis, nuclear translocation of NF-kappaB, and cytokine gene expression and were blocked by caspase inhibition but not by inhibition of IL-1beta signaling. In contrast, Fas-induced macrophage cytokine responses occurred in the absence of apoptosis and were caspase independent, indicating maturation-dependent differences in the Fas signaling pathways that lead to proinflammatory cytokine induction. Rather than contributing to the resolution of inflammation, Fas ligation on circulating monocytes and tissue macrophages may induce proinflammatory cytokine responses that can initiate acute inflammatory responses and tissue injury.