Unité de Pharmacie Galénique, Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium.
Am J Physiol Lung Cell Mol Physiol. 2011 Mar;300(3):L354-61. doi: 10.1152/ajplung.00198.2010. Epub 2010 Dec 3.
Neutrophils constitute the first line of host defense against invading microorganisms. Yet their removal from the inflammatory environment is fundamental for injury restraint and resolution of inflammation. Nicotinamide, a component of vitamin B(3), is known to modulate cell survival. In this study, we assessed the influence of nicotinamide on neutrophil apoptosis, both in vitro and in vivo in a mouse model of endotoxin-induced lung inflammation. In vitro, nicotinamide promoted apoptosis of human blood neutrophils in a dose-dependent manner in the presence of the apoptosis inhibitors granulocyte colony-stimulating factor and granulocyte/macrophage colony-stimulating factor. The highest concentration of nicotinamide completely neutralized the pro-survival effect of granulocyte (macrophage) colony-stimulating factor. Nicotinamide proapoptotic effect was associated with enhanced caspase-3 activity. In addition, nicotinamide slightly reduced neutrophil chemotaxis in vitro. In vivo, pulmonary nicotinamide delivery decreased the levels of cellular and biochemical inflammation markers and increased the percentage of apoptotic neutrophils in bronchoalveolar lavages. Our findings suggest that nicotinamide is an apoptotic stimulus for neutrophils, thereby contributing to the resolution of neutrophilic inflammation in the lungs.
中性粒细胞是宿主防御入侵微生物的第一道防线。然而，将其从炎症环境中清除对于限制损伤和炎症消退至关重要。烟酰胺是维生素 B(3)的一种成分，已知其可调节细胞存活。在这项研究中，我们评估了烟酰胺对脂多糖诱导的肺炎症小鼠模型中体外和体内中性粒细胞凋亡的影响。在体外，烟酰胺在存在凋亡抑制剂粒细胞集落刺激因子和粒细胞/巨噬细胞集落刺激因子的情况下，以剂量依赖性方式促进人血中性粒细胞的凋亡。烟酰胺的最高浓度完全中和了粒细胞（巨噬细胞）集落刺激因子的促生存作用。烟酰胺促凋亡作用与增强的半胱天冬酶-3 活性有关。此外，烟酰胺在体外略微降低了中性粒细胞的趋化性。在体内，肺内烟酰胺给药降低了细胞和生化炎症标志物的水平，并增加了支气管肺泡灌洗液中凋亡中性粒细胞的百分比。我们的研究结果表明，烟酰胺是中性粒细胞的凋亡刺激物，从而有助于肺部中性粒细胞炎症的消退。
