Pulmonary Collectins Play Distinct Roles in Host Defense against Mycobacterium avium
Pulmonary Collectins Play Distinct Roles in Host Defense against Mycobacterium avium
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DOI：
10.4049/jimmunol.1100024
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发表时间：
2011-09-01
影响因子：
4.4
通讯作者：
Kuroki, Yoshio
中科院分区：
文献类型：
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作者：
Ariki, Shigeru;Kojima, Takashi;Kuroki, Yoshio
肺表面活性蛋白A（SP-A）和肺表面活性蛋白D（SP-D）是肺内的两种凝集素，在肺的天然免疫中起重要作用。鸟分枝杆菌是一种能够在巨噬细胞内复制的机会致病菌。我们研究了肺聚集素在宿主防御M中的作用。通过细菌和凝集素之间的直接相互作用实现禽流感感染。虽然两种肺凝集素都与M.这些凝集素以Ca（2+）依赖性的方式与禽流感病毒（Avium）的DNA结合，显示出明显的配体结合特异性和生物活性。SP-A和SP-D分别与含甲氧基的脂质和脂阿拉伯甘露聚糖结合。SP-D结合而SP-A不结合导致M凝集。avium与SP-D的碳水化合物识别结构域的嵌合蛋白，该嵌合体显示类似于SP-A的花束样排列，也凝集M。avium SP-D的糖识别结构域的配体特异性似乎是凝集活性所必需的。SP-A的结合强烈抑制了M.在培养基中培养禽流感病毒。虽然肺凝集素不增加M.他们减弱了细菌的代谢率。扫描电子显微镜下的观察显示，SP-A几乎完全覆盖细菌表面，而SP-D则像散点一样结合在某些区域。这些观察结果表明，一个独特的结合模式的胶原凝集素与它们的生物活性的差异。此外，在SP-D存在下，巨噬细胞吞噬的细菌数量显著增加。这些数据表明，肺凝集素在宿主防御M。avium免疫学杂志，2011，187：2586-2594。
Pulmonary collectins, surfactant protein A (SP-A) and surfactant protein D (SP-D), play important roles in the innate immunity of the lung. Mycobacterium avium is one of the well-known opportunistic pathogens that can replicate within macrophages. We examined the effects of pulmonary collectins in host defense against M. avium infection achieved via direct interaction between bacteria and collectins. Although both pulmonary collectins bound to M. avium in a Ca(2+)-dependent manner, these collectins revealed distinct ligand-binding specificity and biological activities. SP-A and SP-D bound to a methoxy group containing lipid and lipoarabinomannan, respectively. Binding of SP-D but not SP-A resulted in agglutination of M. avium. A chimeric protein with the carbohydrate recognition domain of SP-D, which chimera revealed a bouquet-like arrangement similar to SP-A, also agglutinated M. avium. The ligand specificity of the carbohydrate recognition domain of SP-D seems to be necessary for agglutination activity. The binding of SP-A strongly inhibited the growth of M. avium in culture media. Although pulmonary collectins did not increase membrane permeability of M. avium, they attenuated the metabolic rate of the bacteria. Observations under a scanning electron microscope revealed that SP-A almost completely covers bacterial surfaces, whereas SP-D binds to certain areas like scattered dots. These observations suggest that a distinct binding pattern of collectins correlates with the difference of their biological activities. Furthermore, the number of bacteria phagocytosed by macrophages was significantly increased in the presence of SP-D. These data indicate that pulmonary collectins play critical roles in host defense against M. avium. The Journal of Immunology, 2011, 187: 2586-2594.