Nguyen Hal X, Tidball James G
Department of Physiological Science, University of California, Los Angeles, CA 90095, USA.
J Physiol. 2003 Feb 15;547(Pt 1):125-32. doi: 10.1113/jphysiol.2002.031450. Epub 2002 Dec 20.
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.
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，而微环境部分由炎症细胞及其潜在靶标决定。在本研究中，研究了中性粒细胞、巨噬细胞与可能影响肌肉细胞死亡的肌肉细胞之间的相互作用。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性机制杀死肌肉细胞，而低浓度的一氧化氮（NO）可防止中性粒细胞介导的杀伤。在没有中性粒细胞的情况下，巨噬细胞通过NO依赖性机制杀死肌肉细胞，靶肌肉细胞的存在会使巨噬细胞产生的NO增加三倍，诱导型一氧化氮合酶的浓度没有变化。与中性粒细胞和巨噬细胞以受伤肌肉中观察到的比例共同培养的肌肉细胞，通过NO依赖性、超氧化物非依赖性机制表现出细胞毒性。此外，在使用混合髓样细胞群体而非均匀的中性粒细胞或巨噬细胞群体的实验中，杀死肌肉所需的髓样细胞浓度大大降低。这些研究结果共同表明，肌肉细胞与中性粒细胞之间、肌肉细胞与巨噬细胞之间以及巨噬细胞与中性粒细胞之间的相互作用会改变髓样细胞杀死肌肉细胞的程度和机制。
