Mannose-binding lectin augments the uptake of lipid A, Staphylococcus aureus, and Escherichia coli by Kupffer cells through increased cell surface expression of scavenger receptor A
Mannose-binding lectin augments the uptake of lipid A, Staphylococcus aureus, and Escherichia coli by Kupffer cells through increased cell surface expression of scavenger receptor A
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DOI：
10.4049/jimmunol.177.8.5517
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发表时间：
2006-10-15
影响因子：
4.4
通讯作者：
Kuroki, Yoshio
中科院分区：
文献类型：
--
作者：
Ono, Kei;Nishitani, Chiaki;Kuroki, Yoshio
我们研究了清道夫受体A （SR-A）和甘露糖结合凝集素（MBL）在库普弗细胞摄取内毒素和细菌中的作用。当将[H-3]脂质A注射到小鼠眶后神经丛时，在SR-A缺陷小鼠和与已知的SR-A配体褐藻糖聚糖或乙酰化低密度脂蛋白共注射的野生型小鼠中，肝脏中脂质A的积累明显减少。分离的Kupffer细胞能够以时间依赖性的方式摄取[H-3]脂质A。与野生型细胞相比，来自SR-A缺陷小鼠的非粘附Kupffer细胞相关的脂质A的数量减少了80%，这表明SR-A在Kupffer细胞的内毒素摄取中起重要作用。在rMBL的存在下，Kupffer细胞对脂质A的摄取显著增加。褐藻多糖与[H-3]脂质A共孵育可显著抑制Kupffer细胞对脂质A的基础和mbl刺激摄取。MBL与Kupffer细胞的预孵育也增加了脂质A的摄取。这些结果表明MBL增加了SR-A=介导的Kupffer细胞对脂质A的摄取。一致地，MBL暴露于Kupffer细胞增加了细胞表面SR-A的表达。Kupffer细胞对金黄色葡萄球菌和大肠杆菌的吞噬作用也被MBL与细胞预孵育增强。此外，MBL与脂质A、LPS和金黄色葡萄球菌结合，并沉淀金黄色葡萄球菌。本研究表明SR-A和MBL在Kupffer细胞对内毒素和细菌的摄取中起重要作用。
We investigated roles of scavenger receptor A (SR-A) and mannose-binding lectin (MBL) in the uptake of endotoxin and bacteria by Kupffer cells. When [H-3]lipid A was injected into retro-orbital plexus of mice, significantly less accumulation of lipid A in the liver was observed in SR-A-deficient mice and wild-type mice coinjected with fucoidan or acetylated low-density lipoprotein, which are known ligands for SR-A. Isolated Kupffer cells were able to take up [H-3]lipid A in a time-dependent manner. The amount of lipid A associated with nonadherent Kupffer cells derived from SR-A-deficient mice was reduced by similar to 80% when compared with wild-type cells, indicating an important role of SR-A in endotoxin uptake by Kupffer cells. The lipid A uptake by Kupffer cells was significantly enhanced in the presence of rMBL. Coincubation of fucoidan with [H-3]lipid A significantly inhibited the basal and the MBL-stimulated uptake of lipid A by Kupffer cells. Preincubation of MBL with Kupffer cells also increased the uptake of lipid A. These results indicate that MBL augments the SR-A=mediated uptake of lipid A by Kupffer cells. Consistently, the exposure of MBL to Kupffer cells increased cell surface SR-A expression. The phagocytosis of Staphylococcus aureus and Escherichia coli by Kupffer cells was also enhanced by preincubation of MBL with the cells. In addition, MBL bound to lipid A, LPS, and S. aureus, and precipitated S. aureus. This study demonstrates important roles of SR-A and MBL in the uptake of endotoxin and bacteria by Kupffer cells.