Adams D S, Pero S C, Petro J B, Nathans R, Mackin W M, Wakshull E
Department of Biology/Biotechnology, Worcester Polytechnic Institute, Massachusetts, USA.
J Leukoc Biol. 1997 Dec;62(6):865-73. doi: 10.1002/jlb.62.6.865.
PGG-Glucan (Betafectin) is a novel soluble beta-glucan immunomodulator that enhances leukocyte microbicidal activities without inducing inflammatory cytokines. Although several different receptors for soluble and particulate beta-glucans have been described, the signal transduction pathway(s) used by soluble beta-glucans have not been elucidated. We report that in a murine monocytic cell line (BMC2.3) PGG-Glucan activates nuclear factor-kappaB (NF-kappaB)-like and NF-interleukin-6 (IL-6)-like transcription factors. Electrophoretic mobility shift assays showed that PGG-Glucan activation of the factors is time- and concentration-dependent. The NF-kappaB-like complex includes subunit p65 (rel-A) as one of its components, but apparently not p50 (kappaB1), p52 (kappaB2), p68 (rel-B), or p75 (C-rel) family members. The NF-IL-6-like complex contains subunit C/EBP-beta (NF-IL-6alpha) as one of its components, but apparently not C/EBP-alpha or C/EBP-delta (NF-IL-6beta). As expected, lipopolysaccharide (LPS) activated p65/p50 NF-kappaB and C/EBP-beta NF-IL-6 complexes, increased the nuclear titer of p65 and p50 antigens, and increased cytokine (IL-1beta, tumor necrosis factor alpha) mRNA production. In contrast, PGG-Glucan increased the nuclear titer of p65, but apparently not p50, and did not induce cytokine mRNA production. These data demonstrate that PGG-Glucan utilizes signal transduction pathways different from those used by LPS. The data suggest that activation of the PGG-Glucan-stimulated factors is not sufficient to stimulate cytokine mRNA transcription.
PGG-葡聚糖（β-葡聚糖免疫增强剂）是一种新型可溶性β-葡聚糖免疫调节剂，可增强白细胞杀菌活性，而不诱导炎性细胞因子。尽管已经描述了几种可溶性和颗粒性β-葡聚糖的不同受体，但可溶性β-葡聚糖所使用的信号转导途径尚未阐明。我们报告，在鼠单核细胞系（BMC2.3）中，PGG-葡聚糖激活核因子-κB（NF-κB）样和NF-白细胞介素-6（IL-6）样转录因子。电泳迁移率变动分析表明，PGG-葡聚糖对这些因子的激活具有时间和浓度依赖性。NF-κB样复合物包含亚基p65（rel-A）作为其成分之一，但显然不包含p50（κB1）、p52（κB2）、p68（rel-B）或p75（C-rel）家族成员。NF-IL-6样复合物包含亚基C/EBP-β（NF-IL-6α）作为其成分之一，但显然不包含C/EBP-α或C/EBP-δ（NF-IL-6β）。正如预期的那样，脂多糖（LPS）激活p65/p50 NF-κB和C/EBP-β NF-IL-6复合物，增加p65和p50抗原的核滴度，并增加细胞因子（IL-1β、肿瘤坏死因子α）mRNA的产生。相比之下，PGG-葡聚糖增加p65的核滴度，但显然不增加p50的核滴度，并且不诱导细胞因子mRNA的产生。这些数据表明，PGG-葡聚糖利用的信号转导途径与LPS不同。数据表明，PGG-葡聚糖刺激的因子的激活不足以刺激细胞因子mRNA转录。
