Pulmonary surfactant protein A up-regulates activity of the mannose receptor, a pattern recognition receptor expressed on human macrophages
Pulmonary surfactant protein A up-regulates activity of the mannose receptor, a pattern recognition receptor expressed on human macrophages
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DOI：
10.4049/jimmunol.169.7.3565
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发表时间：
2002-10-01
影响因子：
4.4
通讯作者：
Schlesinger, LS
中科院分区：
文献类型：
--
作者：
Beharka, AA;Gaynor, CD;Schlesinger, LS
吸入的颗粒物和微生物不断地被一系列复杂的肺先天免疫决定因素清除，包括肺泡巨噬细胞（AM）。AM是具有增强的吞噬能力的独特细胞，这部分是由于巨噬细胞甘露糖受体（MR）（各种微生物的模式识别受体）的活性增加。局部因素，“形状”AM功能还没有得到很好的理解。表面活性蛋白A（SP-A）是肺表面活性物质的主要成分，参与先天免疫反应并能增强吞噬作用。在这里，我们表明，SP-A选择性地增强MR表达人单核细胞衍生的巨噬细胞，一个过程涉及的附加糖和SP-A的胶原样结构域。新表达的MR是功能性的。单核细胞衍生的巨噬细胞的SP-A基板上表现出增强的甘露糖BSA的胞饮作用和结核分枝杆菌脂阿拉伯甘露聚糖涂层微球的吞噬作用。新表达的MR可能来自细胞内池，因为：1）SP-A对MR的上调发生在1小时之前，2）新的蛋白质合成对于MR上调不是必需的，以及3）通过MR再循环的甘露糖BSA的胞饮作用增加。来自SP-A（-/-）小鼠的AM相对于SP-A（+/+）具有降低的MR表达。MR活性的SP-A上调提供了增强AM对微生物的吞噬作用的机制，从而增强肺宿主对细胞外病原体的防御，或者矛盾的是，增强细胞内病原体进入其细胞内生态位的潜力。SP-A有助于肺中AM的交替激活状态。
Inhaled particulates and microbes are continually cleared by a complex array of lung innate immune determinants, including alveolar macrophages (AMs). AMs are unique cells with an enhanced capacity for phagocytosis that is due, in part, to increased activity of the macrophage mannose receptor (MR), a pattern recognition receptor for various microorganisms. The local factors that "shape" AM function are not well understood. Surfactant protein A (SP-A), a major component of lung surfactant, participates in the innate immune response and can enhance phagocytosis. Here we show that SP-A selectively enhances MR expression on human monocyte-derived macrophages, a process involving both the attached sugars and collagen-like domain of SP-A. The newly expressed MR is functional. Monocyte-derived macrophages on an SP-A substrate demonstrated enhanced pinocytosis of mannose BSA and phagocytosis of Mycobacterium tuberculosis lipoarabinomannan-coated microspheres. The newly expressed MR likely came from intracellular pools because: 1) up-regulation of the MR by SP-A occurred by 1 h 2) new protein synthesis was not necessary for MR up-regulation, and 3) pinocytosis of mannose BSA via MR recycling was increased. AMs from SP-A(-/-) mice have reduced MR expression relative to SP-A(+/+). SP-A up-regulation of MR activity provides a mechanism for enhanced phagocytosis of microbes by AMs, thereby enhancing lung host defense against extracellular pathogens or, paradoxically, enhancing the potential for intracellular pathogens to enter their intracellular niche. SP-A contributes to the alternative activation state of the AM in the lung.