Neumann N F, Belosevic M
Department of Biological Sciences, University of Alberta, Edmonton, Canada.
Dev Comp Immunol. 1996 Nov-Dec;20(6):427-39. doi: 10.1016/s0145-305x(96)00029-8.
Macrophage activation factors (MAF), induced maximal priming of the respiratory burst response in GMCL after 6 h of stimulus, but by 24 or 48 h no priming effect was observed. Bacterial lipopolysaccharide (LPS) also primed the respiratory burst of goldfish macrophages, but the kinetics of priming were different from that induced by MAF. LPS induced a gradual increase in priming potential over 48 h of cultivation. Co-stimulation of macrophages with MAF and LPS resulted in enhanced priming of respiratory burst activity compared to either factor alone; however, the kinetics of priming were similar to those induced by MAF only. The MAF antagonized the ability of LPS to prime the respiratory burst over extended cultivation. The priming kinetics of the respiratory burst induced by MAF and/or LPS were not unique to GMCL, but were also similar for primary cultures of IVDKM. Respiratory burst deactivated macrophages-mounted potent nitric oxide response, indicating that this deactivation event was selective for respiratory burst activity. Autocrine factors produced by MAF-activated macrophages augmented priming of the respiratory burst, suggesting that deactivation of primed respiratory burst responses was not due to cytokine mediators produced by activated macrophages, but was most likely an intracellular deactivation event. Furthermore, production of reactive intermediates by activated fish macrophages was biphasic; with maximal ROI production occurring 6 h after stimulus, and maximal RNI occurring 72 h after stimulus. Our results indicate that activated fish macrophages mount sequential antimicrobial responses that are selectively deprogrammed once maximal induction has occurred. The ability to selectively deactivate ROI production without affecting subsequent RNI production may play an important role in host defense: regulating the duration of ROI production, and thus minimizing host tissue damage in an otherwise futile attempt to eliminate ROI resistant pathogens.
巨噬细胞激活因子（MAF）在刺激6小时后可诱导金鱼头肾巨噬细胞（GMCL）的呼吸爆发反应达到最大程度的预激发，但在24小时或48小时后未观察到预激发效应。细菌脂多糖（LPS）也可预激发金鱼巨噬细胞的呼吸爆发，但预激发的动力学与MAF诱导的不同。LPS在培养48小时内使预激发潜能逐渐增加。与单独使用任一因子相比，MAF和LPS共同刺激巨噬细胞可增强呼吸爆发活性的预激发；然而，预激发的动力学与仅由MAF诱导的相似。在长时间培养过程中，MAF拮抗LPS预激发呼吸爆发的能力。MAF和/或LPS诱导的呼吸爆发预激发动力学并非GMCL所特有，对于肾间组织巨噬细胞（IVDKM）的原代培养也相似。呼吸爆发失活的巨噬细胞产生有效的一氧化氮反应，表明这种失活事件对呼吸爆发活性具有选择性。MAF激活的巨噬细胞产生的自分泌因子增强了呼吸爆发的预激发，这表明预激发的呼吸爆发反应失活并非由于活化巨噬细胞产生的细胞因子介导，而很可能是一种细胞内失活事件。此外，活化的鱼类巨噬细胞产生反应性中间体是双相的；最大活性氧中间体（ROI）产生发生在刺激后6小时，最大反应性氮中间体（RNI）产生发生在刺激后72小时。我们的结果表明，活化的鱼类巨噬细胞产生相继的抗菌反应，一旦达到最大诱导，这些反应就会被选择性地解除编程。在不影响随后的RNI产生的情况下选择性失活ROI产生的能力可能在宿主防御中起重要作用：调节ROI产生的持续时间，从而在试图消除对ROI有抗性的病原体的徒劳尝试中尽量减少宿主组织损伤。
