PDF(Pubmed)
Abstract：
Pro-inflammatory fungal β-d-glucan (BDG) polysaccharides cause respiratory pathology. However, specific immunological effects of unique BDG structures on pulmonary inflammation are understudied. We characterized the effect of four unique fungal BDGs with unique branching patterns, solubility, and molecular weights in murine airways. Scleroglucan (1 → 3)(1 → 6)-highly branched BDG, laminarin (1 → 3)(1 → 6)-branched BDG, curdlan (1 → 3)-linear BDG, and pustulan (1 → 6)-linear BDG were assessed by nuclear magnetic resonance spectroscopy. Each BDG was tested by inhalation model with C3HeB/FeJ mice and compared to saline-exposed control mice and unexposed sentinels (n = 3-19). Studies were performed ±heat-inactivation (1 h autoclave) to increase BDG solubility. Outcomes included bronchoalveolar lavage (BAL) differential cell counts (macrophages, neutrophils, lymphocytes, eosinophils), cytokines, serum IgE, and IgG2a (multiplex and ELISA). Ex vivo primary cells removed from lungs and plated at monolayer were stimulated (BDG, lipopolysaccharide (LPS), anti-CD3), and cytokines compared to unstimulated cells. Right lung histology was performed. Inhalation of BDGs with distinct branching patterns exhibited varying inflammatory potency and immunogenicity. Lichen-derived (1 → 6)-linear pustulan was the most pro-inflammatory BDG, increasing inflammatory infiltrate (BAL), serum IgE and IgG2a, and cytokine production. Primed lung cells responded to secondary LPS stimulation with a T-cell-specific response to pustulan. Glucan source and solubility should be considered in exposure and toxicological studies.
摘要：
促炎真菌β-d-葡聚糖(BDG)多糖引起呼吸道病理学。然而,独特的BDG结构对肺部炎症的特异性免疫效应研究不足。我们表征了具有独特分支模式的四种独特真菌BDG的效果，溶解度，和小鼠气道的分子量。硬葡聚糖（1→3）（1→6）-高度分支的BDG，laminarin(1→3)(1→6)-分枝BDG，Curdlan(1→3)-线性BDG，和pustulan（1→6）-线性BDG通过核磁共振波谱进行评估。用C3HeB/FeJ小鼠通过吸入模型测试每个BDG,并与暴露于盐水的对照小鼠和未暴露的前哨(n=3-19)进行比较。进行±热灭活(1小时高压釜)以增加BDG溶解度的研究。结果包括支气管肺泡灌洗（BAL）差异细胞计数（巨噬细胞，中性粒细胞，淋巴细胞，嗜酸性粒细胞)，细胞因子,血清IgE,和IgG2a(多重和ELISA)。刺激从肺中取出并铺在单层的离体原代细胞(BDG，脂多糖（LPS），抗CD3)，和细胞因子与未刺激的细胞相比。进行右肺组织学检查。具有不同分支模式的BDG的吸入表现出不同的炎症效力和免疫原性。苔藓来源的(1→6)-线性脓疱素是最促炎的BDG，增加炎症浸润（BAL），血清IgE和IgG2a,和细胞因子的产生。引发的肺细胞对次级LPS刺激有反应，对pustulan有T细胞特异性反应。在暴露和毒理学研究中应考虑葡聚糖的来源和溶解度。
