Pulmonary surfactant protein A mediates enhanced phagocytosis of Mycobacterium tuberculosis by a direct interaction with human macrophages.
Pulmonary surfactant protein A mediates enhanced phagocytosis of Mycobacterium tuberculosis by a direct interaction with human macrophages.
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DOI：
10.4049/jimmunol.155.11.5343
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发表时间：
1995-12
影响因子：
4.4
通讯作者：
C. D. Gaynor;F. X. McCormack;D. Voelker;S. McGowan;L. Schlesinger
中科院分区：
文献类型：
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作者：
C. D. Gaynor;F. X. McCormack;D. Voelker;S. McGowan;L. Schlesinger
在结核分枝杆菌的初始感染期间，到达肺的远端气隙的细菌在肺表面活性剂存在的情况下被肺泡巨噬细胞吞噬。在此，我们研究了表面活性物质相关蛋白A（SP-A）在巨噬细胞毒Erdman株吞噬作用中的作用。通过人单核细胞衍生的巨噬细胞（MDM）和人肺泡巨噬细胞（HAM）对结核病进行治疗。用肺泡蛋白沉积症患者的可溶性SP-A（APP SP-A4）和重组大鼠SP-A（SP-Ahyp）孵育的巨噬细胞单层显示M.结核病，分别为82 +/- 17%和49 +/-18%。在加入细菌之前通过洗涤从单层去除SP-A并没有减少增强的粘附。荧光显微镜检查表明，洗过的单层细胞含有细胞内，而不是表面结合的SP-A。这些研究表明SP-A和巨噬细胞之间的直接相互作用介导了M.结核与这种解释一致，在人或大鼠SP-A（底物SP-A）上形成的巨噬细胞单层显示出M的粘附增强。肺结核的顶面（APP SP-A和本地大鼠SP-A增加M.结核病依从性分别为102 +/- 16%和102 +/-25%）。电子显微镜检查显示APP SP-A处理的MDM横截面中吞噬细菌的数量增加。缺乏碳水化合物的SP-A蛋白不能增强M。结核粘附于巨噬细胞。与此相反，热变性APP SP-A增强粘附细菌相当于完整的糖蛋白。因此，SP-A的碳水化合物部分似乎在SP-A-巨噬细胞相互作用中是关键的。最后，甘露聚糖和抗甘露糖受体抗体完全抑制M.用APP SP-A观察到的结核病，提供了巨噬细胞甘露糖受体活性上调的证据。这些研究暗示SP-A是肺泡巨噬细胞功能的重要调节剂，导致M。结核病获得进入其细胞内的利基。
During initial infection with Mycobacterium tuberculosis, bacteria that reach the distal airspaces of the lung are phagocytosed by alveolar macrophages in the presence of pulmonary surfactant. Here we have examined the role of surfactant-associated protein A (SP-A) in phagocytosis of the virulent Erdman strain of M. tuberculosis by human monocyte-derived macrophages (MDMs) and human alveolar macrophages (HAMs). Macrophage monolayers incubated with soluble SP-A from alveolar proteinosis patients (APP SP-A4) and recombinant rat SP-A (SP-Ahyp) demonstrated enhanced adherence of M. tuberculosis, 82 +/- 17% and 49 +/- 18%, respectively. Removal of SP-A from monolayers by washing before adding bacteria did not diminish the enhanced adherence. Fluorescence microscopy demonstrated that washed monolayers contained intracellular rather than surface-bound SP-A. These studies indicated a direct interaction between SP-A and the macrophage in mediating enhanced adherence of M. tuberculosis. Consistent with this interpretation, macrophage monolayers formed on human or rat SP-A (substrate SP-A) demonstrated enhanced adherence of M. tuberculosis to their apical surface (APP SP-A and native rat SP-A increased M. tuberculosis adherence by 102 +/- 16% and 102 +/- 25%, respectively). Electron microscopy demonstrated increased numbers of phagocytosed bacteria in APP SP-A-treated MDM cross-sections. SP-A proteins devoid of carbohydrate failed to enhance M. tuberculosis adherence to macrophages. In contrast, heat-denatured APP SP-A enhanced adherence of bacteria equivalent to that of intact glycoprotein. Thus, the carbohydrate moieties of SP-A appear to be critical in the SP-A-macrophage interaction. Finally, mannan and anti-mannose receptor Ab completely inhibited the enhanced phagocytosis of M. tuberculosis observed with APP SP-A, providing evidence for up-regulation of macrophage mannose receptor activity. These studies implicate SP-A as an important modulator of alveolar macrophage function that results in an enhanced potential for M. tuberculosis to gain access to its intracellular niche.