CD11/CD18 and CD14 share a common lipid A signaling pathway.
CD11/CD18 and CD14 share a common lipid A signaling pathway.
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DOI：
10.4049/jimmunol.161.10.5413
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发表时间：
1998-11
影响因子：
4.4
通讯作者：
R. Ingalls;Brian G. Monks;R. Savedra;W. Christ;R. Delude;A. Medvedev;T. Espevik;D. Golenbock
中科院分区：
文献类型：
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作者：
R. Ingalls;Brian G. Monks;R. Savedra;W. Christ;R. Delude;A. Medvedev;T. Espevik;D. Golenbock
LPS的脂质A部分对吞噬细胞的激活与革兰氏阴性脓毒症的发病机制有关。虽然两种LPS受体，CD 14和CD 11/CD 18，已经与细胞信号转导，LPS信号转导级联的细节仍然不清楚。作为GPI锚定的可溶性蛋白存在的CD 14缺乏胞质信号传导结构域，这表明需要辅助分子来激活细胞。CD 11/CD 18整合素是跨膜蛋白。与CD 14一样，当在仓鼠成纤维细胞中国仓鼠卵巢（CHO）-K1表面表达时，它们能够介导LPS诱导的细胞活化。细胞质缺失突变体仍然能够激活转染的CHO-K1的观察结果表明，CD 11/CD 18也利用了相关的信号转导。我们试图确定CD 14和CD 11/CD 18所利用的信号系统之间的进一步相似性。LPS结合蛋白可将LPS转移至CD 14，增强LPS诱导的细胞活化和CD 11/CD 18转染的CHO-K1中革兰氏阴性菌的结合，因此暗示LPS结合蛋白也可将LPS转移至CD 11/CD 18。当分析合成的脂质A类似物在CHO转染子中作为LPS激动剂或拮抗剂的能力时，我们发现无论表达哪种LPS受体，效果都是相同的。这支持了这样的假设，即与CD 14和CD 11/CD 18不同的受体负责区分LPS的脂质A和LPS拮抗剂。我们建议，这种受体，这是LPS拮抗剂的目标，作为真正的信号转导在LPS诱导的细胞活化CD 14和CD 11/CD 18。
The activation of phagocytes by the lipid A moiety of LPS has been implicated in the pathogenesis of Gram-negative sepsis. While two LPS receptors, CD14 and CD11/CD18, have been associated with cell signaling, details of the LPS signal transduction cascade remain obscure. CD14, which exists as a GPI-anchored and a soluble protein, lacks cytoplasmic-signaling domains, suggesting that an ancillary molecule is required to activate cells. The CD11/CD18 integrins are transmembrane proteins. Like CD14, they are capable of mediating LPS-induced cellular activation when expressed on the surface of hamster fibroblasts Chinese hamster ovary (CHO)-K1. The observation that a cytoplasmic deletion mutant is still capable of activating transfected CHO-K1 argues that CD11/CD18 also utilizes an associated signal transducer. We sought to identify further similarities between the signaling systems utilized by CD14 and CD11/CD18. LPS-binding protein, which transfers LPS to CD14, enhanced both LPS-induced cellular activation and binding of Gram-negative bacteria in CD11/CD18-transfected CHO-K1, thus implying that LPS-binding protein can also transfer LPS to CD11/CD18. When synthetic lipid A analogues were analyzed for their ability to function as LPS agonists, or antagonists, in the CHO transfectants, we found the effects were identical regardless of which LPS receptor was expressed. This supports the hypothesis that a receptor distinct from CD14 and CD11/CD18 is responsible for discriminating between the lipid A of LPS and the LPS antagonists. We propose that this receptor, which is the target of the LPS antagonists, functions as the true signal transducer in LPS-induced cellular activation for both CD14 and CD11/CD18.