Macrophage-neutrophil interaction: A paradigm for chronic inflammation revisited
Macrophage-neutrophil interaction: A paradigm for chronic inflammation revisited
复制标题
DOI：
10.1046/j.1440-1711.2001.01020.x
复制
发表时间：
2001-09-01
影响因子：
4
通讯作者：
Lefkowitz, SS
中科院分区：
文献类型：
--
作者：
Lefkowitz, DL;Lefkowitz, SS
巨噬细胞已被描述为促炎细胞因子的“工厂”。几年前，目前的研究者报道了失活的髓过氧化物酶（iMPO）与巨噬细胞甘露糖受体的结合导致TNF和其他细胞因子的诱导。此外，如果内皮细胞与iMPO一起孵育，但不与酶活性髓过氧化物酶（MPO）一起孵育，则观察到细胞因子mRNA和细胞因子的上调。从整体上看，这些数据表明髓过氧化物酶功能的二分法;即，酶活性MPO主要通过“细胞毒性三联体”在细胞杀伤中发挥作用，而iMPO通过诱导多种细胞因子发挥免疫调节分子的作用。这些研究强调了先前未被认识到的中性粒细胞、内皮细胞和巨噬细胞之间的相互作用，导致TNF的诱导和炎症的持续。诱导的炎症可能与许多疾病相关，其中中性粒细胞发挥重要作用。这种相互作用在类风湿性关节炎发病机制中的重要性目前正在研究中。
Macrophages have been described as 'factories' of pro-inflammatory cytokines. Several years ago the present investigators reported that binding of inactive myeloperoxidase (iMPO) to the macrophage-mannose receptor resulted in the induction of TNF and other cytokines. Also, if endothelial cells were incubated with iMPO, but not enzymatically active myeloperoxidase (MPO), upregulation of cytokine mRNA and cytokines was observed. Taken in their entirety, the data suggest a dichotomy of function for myeloperoxidase; that is, enzymatically active MPO functions primarily in cell killing through the 'cytotoxic triad' and iMPO functions as an immunoregulatory molecule through the induction of numerous cytokines. These studies underscore a previously unrecognized interaction among neutrophils, endothelial cells and macrophages, resulting in the induction of TNF and perpetuation of inflammation. The inflammation induced could be relevant in a number of diseases in which neutrophils play a prominent role. The importance of this interaction in the pathogenesis of rheumatoid arthritis is currently under investigation.