Surfactant protein D binds to Mycobacterium tuberculosis bacilli and lipoarabinomannan via carbohydrate-lectin interactions resulting in reduced phagocytosis of the bacteria by macrophages.
Surfactant protein D binds to Mycobacterium tuberculosis bacilli and lipoarabinomannan via carbohydrate-lectin interactions resulting in reduced phagocytosis of the bacteria by macrophages.
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发表时间：
1999
影响因子：
4.4
通讯作者：
J. Ferguson;D. Voelker;F. McCormack;L. Schlesinger
中科院分区：
文献类型：
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作者：
J. Ferguson;D. Voelker;F. McCormack;L. Schlesinger
表面活性蛋白-D（SurfactantProtein-D，SP-D）是一种在肺远端产生的聚集蛋白，在先天性肺免疫中起重要作用。对结核分枝杆菌（M.tb）的初始免疫应答在肺中特别重要，因为这种吸入的病原体进入肺泡巨噬细胞是疾病发病机制中的关键事件。在这里，我们研究了SP-D与结核分枝杆菌的结合以及这种结合对结核分枝杆菌粘附的影响。结核杆菌感染人类巨噬细胞。这些研究表明SP-D与结核分枝杆菌的特异性结合是可饱和的、钙依赖性的和碳水化合物可降解的。除了纯化的SP-D外，来自健康供体和肺泡蛋白沉积症患者的支气管肺泡灌洗液中的SP-D也与结核分枝杆菌结合。结核分枝杆菌与SP-D孵育导致细菌凝集。与其与结核分枝杆菌的结合相反，SP-D与无毒耻垢分枝杆菌的结合最低。SP-D主要结合来自结核分枝杆菌的毒性Erdman菌株的脂阿拉伯甘露聚糖，但不结合来自结核分枝杆菌的脂阿拉伯甘露聚糖。恶臭SP-D与Erdman脂阿拉伯甘露聚糖的结合由该脂聚糖的末端甘露糖基寡糖介导。结核分枝杆菌与亚凝集浓度的SP-D孵育导致细菌对巨噬细胞的粘附减少（对照粘附的62.7%+/-3.3%SEM，n = 8），而细菌与表面活性蛋白A孵育导致对单核细胞衍生的巨噬细胞的粘附显著增加。这些数据为SP-D与M的特异性结合提供了证据。肺结核和表明SP-D和表面活性蛋白A在先天宿主对肺中该病原体的反应中起不同的作用。
Surfactant protein-D (SP-D) is a collectin produced in the distal lung airspaces that is believed to play an important role in innate pulmonary immunity. Naive immunologic responses to Mycobacterium tuberculosis (M.tb) are especially important in the lung, since entry of this inhaled pathogen into the alveolar macrophage is a pivotal event in disease pathogenesis. Here we investigated SP-D binding to M.tb and the effect of this binding on the adherence of M. tb to human macrophages. These studies demonstrate specific binding of SP-D to M.tb that is saturable, calcium dependent, and carbohydrate inhibitable. In addition to purified SP-D, SP-D in bronchoalveolar lavage fluids from healthy donors and patients with alveolar proteinosis also binds to M.tb. Incubation of M.tb with SP-D results in agglutination of the bacteria. In contrast to its binding to M.tb, SP-D binds minimally to the avirulent Mycobacterium smegmatis. SP-D binds predominantly to lipoarabinomannan from the virulent Erdman strain of M.tb, but not the lipoarabinomannan from M. smegmatis. The binding of SP-D to Erdman lipoarabinomannan is mediated by the terminal mannosyl oligosaccharides of this lipoglycan. Incubation of M.tb with subagglutinating concentrations of SP-D leads to reduced adherence of the bacteria to macrophages (62.7% of control adherence +/- 3.3% SEM, n = 8), whereas incubation of bacteria with surfactant protein A leads to significantly increased adherence to monocyte-derived macrophages. These data provide evidence for specific binding of SP-D to M. tuberculosis and indicate that SP-D and surfactant protein A serve different roles in the innate host response to this pathogen in the lung.