Interactions between neutrophils and macrophages promote macrophage killing of rat muscle cells in vitro
Interactions between neutrophils and macrophages promote macrophage killing of rat muscle cells in vitro
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DOI：
10.1113/jphysiol.2002.031450
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发表时间：
2003-02-15
影响因子：
5.5
通讯作者：
Tidball, JG
中科院分区：
文献类型：
--
作者：
Nguyen, HX;Tidball, JG
目前的证据表明，炎症细胞的生理功能对其微环境高度敏感，这在一定程度上是由炎症细胞及其潜在靶点决定的。在目前的研究中，中性粒细胞、巨噬细胞和肌肉细胞之间的相互作用可能会影响肌肉细胞的死亡。研究结果表明，在没有巨噬细胞的情况下，中性粒细胞在体外通过超氧化物依赖的机制杀死肌肉细胞，低浓度的一氧化氮(NO)对中性粒细胞介导的杀伤具有保护作用。在没有中性粒细胞的情况下，巨噬细胞通过NO依赖的机制杀死肌肉细胞，靶肌肉细胞的存在导致巨噬细胞产生的NO增加三倍，而诱导型一氧化氮合酶的浓度没有变化。肌肉细胞与中性粒细胞和巨噬细胞按损伤肌肉中观察到的比例共同培养，通过NO依赖、超氧化物歧化的机制显示出细胞毒性。此外，在使用混合的髓系细胞群而不是统一的中性粒细胞或巨噬细胞群的检测中，肌肉杀伤所需的髓系细胞的浓度大大降低。这些发现共同表明，髓系细胞对肌肉细胞的杀伤大小和机制受到肌肉细胞和中性粒细胞之间、肌肉细胞和巨噬细胞之间以及巨噬细胞和中性粒细胞之间相互作用的影响。
Current evidence indicates that the physiological functions of inflammatory cells are highly sensitive to their microenvironment, which is partially determined by the inflammatory cells and their potential targets. In the present investigation, interactions between neutrophils, macrophages and muscle cells that may influence muscle cell death are examined. Findings show that in the absence of macrophages, neutrophils kill muscle cells in vitro by superoxide-dependent mechanisms, and that low concentrations of nitric oxide (NO) protect against neutrophil-mediated killing. In the absence of neutrophils, macrophages kill muscle cells through a NO-dependent mechanism, and the presence of target muscle cells causes a three-fold increase in NO production by macrophages, with no change in the concentration of inducible nitric oxide synthase. Muscle cells that are co-cultured with both neutrophils and macrophages in proportions that are observed in injured muscle show cytotoxicity through a NO-dependent, superoxide-independent mechanism. Furthermore, the concentration of myeloid cells that is necessary for muscle killing is greatly reduced in assays that use mixed myeloid cell populations, rather than uniform populations of neutrophils or macrophages. These findings collectively show that the magnitude and mechanism of muscle cell killing by myeloid cells are modified by interactions between muscle cells and neutrophils, between muscle cells and macrophages and between macrophages and neutrophils.