Young Shih-Houng, Robinson Victor A, Barger Mark, Frazer David G, Castranova Vincent, Jacobs Robert R
Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, West Virginia, USA.
J Toxicol Environ Health A. 2003 Mar 28;66(6):551-63. doi: 10.1080/15287390306355.
1-->3-beta-Glucans produce pulmonary inflammation in rats and are commonly found in indoor air dust samples. Conformation is an important factor determining the biological activity of 1-->3-beta-glucans. The partially opened triple-helix conformation induced by NaOH treatment and the annealed triple-helix conformation have been identified by fluorescence resonance energy transfer spectroscopy in our previous study. The objective of this study was to examine the role of these conformations of 1-->3-beta-glucans in the induction of pulmonary inflammation in rats. A partially opened triple-helix conformation of the known inflammatory 1-->3-beta-glucan zymosan was prepared by treating zymosan with NaOH followed by neutralization and dialysis. The annealed triple-helix conformation was prepared by allowing the partially opened triple-helix conformation to anneal for 9 d at room temperature. Rats were exposed to fresh or annealed NaOH-treated zymosan via intratracheal instillation. The results show that the zymosan-induced pulmonary inflammatory responses were significantly reduced after the 9-d annealing period, which suggests that this inflammatory response was dependent on the conformation of zymosan. Freezing NaOH-treated zymosan (for 7 d) inhibited the annealing process. Exposure of rats to thawed preparations of zymosan resulted in the same inflammatory responses as the freshly prepared partially opened triple-helix zymosan. In contrast, the potency of untreated zymosan did not change significantly following a 7-d annealing period, indicating that annealing occurs only after the conformation has been modified by NaOH treatment. This study indicates that the partially opened triple helix of 1-->3-beta-glucans is more active than the closed conformation in inducing pulmonary inflammation in rats.
1,3-β-葡聚糖可在大鼠体内引发肺部炎症,且常见于室内空气灰尘样本中。构象是决定1,3-β-葡聚糖生物活性的一个重要因素。在我们之前的研究中,通过荧光共振能量转移光谱法已鉴定出由氢氧化钠处理诱导产生的部分开放三螺旋构象以及退火后的三螺旋构象。本研究的目的是探讨1,3-β-葡聚糖的这些构象在诱导大鼠肺部炎症中的作用。通过用氢氧化钠处理酵母聚糖,随后进行中和及透析,制备出已知具有炎症性的1,3-β-葡聚糖酵母聚糖的部分开放三螺旋构象。通过让部分开放的三螺旋构象在室温下退火9天来制备退火后的三螺旋构象。大鼠通过气管内滴注暴露于新鲜的或退火后的经氢氧化钠处理的酵母聚糖中。结果表明,经过9天的退火期后,酵母聚糖诱导的肺部炎症反应显著降低,这表明这种炎症反应取决于酵母聚糖的构象。冷冻经氢氧化钠处理的酵母聚糖(7天)会抑制退火过程。将大鼠暴露于解冻后的酵母聚糖制剂中会产生与新鲜制备的部分开放三螺旋酵母聚糖相同的炎症反应。相比之下,未处理的酵母聚糖在经过7天的退火期后效力没有显著变化,这表明退火仅在构象经氢氧化钠处理修饰后才会发生。本研究表明,1,3-β-葡聚糖的部分开放三螺旋在诱导大鼠肺部炎症方面比封闭构象更具活性。