Prolonged reduction of leukocyte membrane-associated Dectin-1 levels following β-glucan administration
Prolonged reduction of leukocyte membrane-associated Dectin-1 levels following β-glucan administration
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DOI：
10.1124/jpet.106.102293
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发表时间：
2006-08-01
影响因子：
3.5
通讯作者：
Williams, David L.
中科院分区：
文献类型：
--
作者：
Ozment-Skelton, Tammy R.;Goldman, Matthew P.;Williams, David L.
Dectin-1是真菌葡聚糖的主要模式识别受体。Dectin-1介导对葡聚糖的内化和生物反应。我们研究了i的影响。V或I。注射后3小时至10天，磷酸葡聚糖（GP）给药对小鼠外周血白细胞、脾细胞、骨髓和腹膜细胞中Dectin-1膜表达的影响。还检查了循环白细胞对血液中葡聚糖的摄取和内化。荧光标记的GP被循环外周血白细胞、脾细胞和腹膜细胞从体循环中摄取。在内化之后，葡聚糖与Dectin-1共定位在细胞内囊泡中。单次胃肠外注射GP导致外周白细胞膜相关Dectin-1阳性显著降低（类似于33-85%），持续长达7天。GP给药后白细胞膜相关Dectin-1的损失主要是由于中性粒细胞和单核细胞膜上Dectin-1水平降低，血液中循环的中性粒细胞或单核细胞的百分比没有显著变化。施用对照碳水化合物聚合物，即，不是Dectin-1配体的甘露聚糖或普鲁兰多糖不降低Dectin-1白细胞阳性，表明对Dectin-1的作用是葡聚糖特异性的。事实上，甘露聚糖给药增加了白细胞Dectin-1阳性，因此证明了与GP相比对白细胞Dectin-1的差异效应。我们的结论是，GP的全身给药对白细胞膜Dectin-1阳性的丧失具有特异性和长期的影响。这些数据可能对开发免疫调节碳水化合物的给药方案具有重要意义。
Dectin-1 is the primary pattern recognition receptor for fungal glucans. Dectin-1 mediates the internalization and biological response to glucans. We examined the effect of i. v. or i. p. glucan phosphate (GP) administration on Dectin-1 membrane expression in murine peripheral blood leukocytes, splenocytes, bone marrow, and peritoneal cells from 3 h to 10 days after injection. Circulating leukocytes were also examined for uptake and internalization of glucans from the blood. Fluorescent-labeled GP was taken up from the systemic circulation by circulating peripheral leukocytes, splenocytes, and peritoneal cells. Following internalization, glucan colocalized with Dectin-1 in an intracellular vesicle. A single parenteral injection of GP resulted in a significant reduction (similar to 33-85%) in peripheral leukocyte membrane-associated Dectin-1 positivity that lasted for up to 7 days. The loss of leukocyte membrane-associated Dectin-1 after GP administration was primarily due to decreased levels of Dectin-1 on neutrophil and monocyte membranes with no significant changes in the percentage of neutrophils or monocytes circulating in the blood. Administration of control carbohydrate polymers, i.e., mannan or pullulan, which are not ligands for Dectin-1, did not decrease Dectin-1 leukocyte positivity, indicating that the effect on Dectin-1 is specific to glucans. In fact, mannan administration increased leukocyte Dectin-1 positivity, thus demonstrating a differential effect on leukocyte Dectin-1, compared with GP. We conclude that systemic administration of GP has a specific and prolonged effect on loss of leukocyte membrane Dectin-1 positivity. These data may have important implications for developing dosing regimens for immunomodulatory carbohydrates.