Wang Zhengdong, Schwab Ute, Rhoades Elizabeth, Chess Patricia R, Russell David G, Notter Robert H
Department of Pediatrics, University of Rochester School of Medicine, Box 850, 601 Elmwood Avenue, Rochester, NY 14642, USA.
Tuberculosis (Edinb). 2008 May;88(3):178-86. doi: 10.1016/j.tube.2007.11.003. Epub 2007 Dec 21.
The transmission of Mycobacterium tuberculosis (TB) requires extensive damage to the lungs to facilitate bacterial release into the airways, and it is therefore likely that the microorganism has evolved mechanisms to exacerbate its local pathology. This study examines the inhibitory effects of lipids extracted and purified chromatographically from TB on the surface-active function of lavaged bovine lung surfactant (LS) and a clinically relevant calf lung surfactant extract (CLSE). Total lipids from TB greatly inhibited the surface activity of LS and CLSE on the pulsating bubble surfactometer at physical conditions applicable for respiration in vivo (37 degrees C, 20 cycles/min, 50% area compression). Minimum surface tensions for LS (0.5 mg/ml) and CLSE (1 mg/ml) were raised from <1 mN/m to 15.7+/-1.2 and 18.7+/-1.3 mN/m after 5 min of bubble pulsation in the presence of total TB lipids (0.15 mg/ml). TB mixed waxes (0.15 mg/ml) and TB trehalose monomycolates (TMMs, 0.15 mg/ml) also significantly inhibited the surface activity of LS and CLSE (minimum surface tensions of 10-16 mN/m after 5 min of bubble pulsation), as did purified trehalose 6,6'-dimycolate (TDM, cord factor). Phosphatidylinositol mannosides (PIMs, 0.15 mg/ml) from TB had no inhibitory effect on the surface activity of LS or CLSE. Concentration dependence studies showed that LS was also inhibited significantly by total TB lipids at 0.075 mg/ml, with a smaller activity decrease apparent even at 0.00375 mg/ml. These findings document that TB contains multiple lipids that can directly impair the biophysical function of endogenous and exogenous lung surfactants. Direct inhibition by TB lipids could worsen surfactant dysfunction caused by plasma proteins or other endogenous substances induced by inflammatory injury in the infected lungs. TB lipids could also inhibit the effectiveness of exogenous surfactants used to treat severe acute respiratory failure in TB patients meeting criteria for clinical acute lung injury (ALI) or the acute respiratory distress syndrome (ARDS).
结核分枝杆菌（TB）的传播需要肺部受到广泛损伤，以便细菌释放到气道中，因此这种微生物很可能已经进化出加剧其局部病理的机制。本研究考察了通过色谱法从结核分枝杆菌中提取和纯化的脂质对灌洗得到的牛肺表面活性剂（LS）以及临床相关的小牛肺表面活性剂提取物（CLSE）表面活性功能的抑制作用。在适用于体内呼吸的物理条件（37℃、20次/分钟、50%面积压缩）下，结核分枝杆菌的总脂质在脉动气泡表面张力仪上极大地抑制了LS和CLSE的表面活性。在存在结核分枝杆菌总脂质（0.15mg/ml）的情况下，气泡脉动5分钟后，LS（0.5mg/ml）和CLSE（1mg/ml）的最小表面张力从<1mN/m分别提高到15.7±1.2mN/m和18.7±1.3mN/m。结核分枝杆菌混合蜡质（0.15mg/ml）和结核分枝杆菌海藻糖单霉菌酸酯（TMMs，0.15mg/ml）也显著抑制了LS和CLSE的表面活性（气泡脉动5分钟后的最小表面张力为10 - 16mN/m），纯化的海藻糖6,6'-二霉菌酸酯（TDM，索状因子）也是如此。结核分枝杆菌的磷脂酰肌醇甘露糖苷（PIMs，0.15mg/ml）对LS或CLSE的表面活性没有抑制作用。浓度依赖性研究表明，结核分枝杆菌总脂质在0.075mg/ml时也能显著抑制LS，即使在0.00375mg/ml时也有较小的活性降低。这些发现证明结核分枝杆菌含有多种能够直接损害内源性和外源性肺表面活性剂生物物理功能的脂质。结核分枝杆菌脂质的直接抑制作用可能会使由血浆蛋白或感染肺部炎症损伤诱导的其他内源性物质引起的表面活性剂功能障碍恶化。结核分枝杆菌脂质还可能抑制用于治疗符合临床急性肺损伤（ALI）或急性呼吸窘迫综合征（ARDS）标准的结核病患者严重急性呼吸衰竭的外源性表面活性剂的有效性。
