Surfactant proteins A and D bind CD14 by different mechanisms
Surfactant proteins A and D bind CD14 by different mechanisms
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DOI：
10.1074/jbc.m001107200
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发表时间：
2000-07-21
影响因子：
4.8
通讯作者：
Kuroki, Y
中科院分区：
文献类型：
--
作者：
Sano, H;Chiba, H;Kuroki, Y
表面活性剂蛋白A（SP-A）和D（SP-D）是肺凝集素，其是肺的先天免疫系统的成分。最近的证据（佐野，H.，Sohma，H.，穆塔，T.，Nomura，S.，Voelker，D. R.，和Kuroki，Y.（1999）J.Immunol.163，387-395）证明SP-A通过与CD 14的直接相互作用调节脂多糖（LPS）诱导的细胞应答。在这份报告中，我们研究了参与CD 14识别的肺聚集蛋白的结构元件和CD 14/LPS相互作用的后果。大鼠SP-A和SP-D以浓度依赖性方式结合CD 14。甘露糖和EDTA抑制SP-D与CD 14的结合，但不降低SP-A的结合。SP-A与CD 14的结合被结合SP-A颈结构域的单克隆抗体完全阻断，但仅被结合SP-A凝集素结构域的抗体部分阻断。SP-A而非SP-D与去糖基化的CD 14结合，SP-D降低CD 14与光滑和粗糙LPS的结合，而SP-A增强CD 14与粗糙LPS的结合并抑制与光滑LPS的结合。SP-A还改变了CD 14存在下LPS在蔗糖密度梯度上的迁移曲线。根据这些结果，我们得出结论：1）肺凝集素结合CD 14，2）SP-A颈结构域和SP-D凝集素结构域参与CD 14结合，3）SP-A识别CD 14的肽组分，SP-D识别CD 14的碳水化合物部分，和4）肺凝集素改变LPS/CD 14相互作用。
Surfactant proteins A (SP-A) and D (SP-D) are lung collectins that are constituents of the innate immune system of the lung. Recent evidence (Sano, H,, Sohma, H,, Muta, T., Nomura, S., Voelker, D. R., and Kuroki, Y. (1999) J. Immunol. 163, 387-395) demonstrates that SP-A modulates lipopolysaccharide (LPS)-induced cellular responses by direct interaction with CD14. In this report we examined the structural elements of the lung collectins involved in CD14 recognition and the consequences for CD14/LPS interaction. Rat SP-A and SP-D bound CD14 in a concentration-dependent manner. Mannose and EDTA inhibited SP-D binding to CD14 but did not decrease SP-A binding. The SP-A binding to CD14 was completely blocked by a monoclonal antibody that binds to the SP-A neck domain but only partially blocked by an antibody that binds to the SP-A lectin domain. SP-A but not SP-D bound to deglycosylated CD14, SP-D decreased CD14 binding to both smooth and rough LPS, whereas SP-A enhanced CD14 binding to rough LPS and inhibited binding to smooth LPS. SP-A also altered the migration profile of LPS on a sucrose density gradient in the presence of CD14. From these results, we conclude that 1) lung collectins bind CD14, 2) the SP-A neck domain and SP-D lectin domain participate in CD14 binding, 3) SP-A recognizes a peptide component and SP-D recognizes a carbohydrate moiety of CD14, and 4) lung collectins alter LPS/CD14 interactions.