Role of CD14 in bacterial infection, and search and regulation of molecules in early signal transduction

尽管缺乏对内毒素的促炎反应，但CD14缺陷小鼠清除大肠杆菌的效率至少是正常小鼠的10倍。在这项研究中，我们表明，这是由于在CD14缺陷小鼠注射革兰氏阴性菌或内毒素后，PMN早期和强烈的募集；相反，在正常小鼠中，PMN的渗透延迟了24小时。在Toll样受体(TLR)4缺陷的小鼠中，也看到了类似的结果，即内毒素诱导的PMN早期渗透和增强对大肠杆菌的清除。此外，脂蛋白A部分不仅能诱导CD14缺陷和TLR-4缺陷小鼠的PMN早期浸润，而且在正常小鼠中也能诱导PMN的早期浸润。综上所述，脂蛋白A组分刺激CD14和TLR4不依赖于CD14和TLR4的独特而关键的先天免疫反应途径，导致PMN的早期渗透和细菌的清除，获得了在α-抗胰蛋白酶启动子控制下分泌小鼠CD14氨基端71个氨基酸的转基因小鼠。小鼠对全身性致死性Shwartzman反应有明显的抵抗力。通过pharge展示分析，筛选出了一个与细胞表面早期信号转导有关的候选蛋白。

Despite the lack of a proinflammatory response to LPS, CD14-deficient mice clear E.coli at least 10 times more efficiently than normal mice. In this study, we show that this is due to an early and intense recruitment of PMN following the injection of Gram-negative bacteria or LPS in CD14-deficient mice ; in contrast, PMN infiltration is delayed by 24 h in normal mice. Similar results of early LPS-induced PMN infiltration and enhanced clearance of E.coli were seen in Toll-like receptor (TLR) 4-deficient mice. Furthermore, the lipid A moiety of LPS induced early PMN infiltration not only in CD14-deficient and TLR-4-deficient mice, but also in normal mice. In conclusion, the lipid A component of LPS stimulates a unique and critical pathway of innate immune responses that is independent of CD14 and TLR4 and results in early PMN infiltration and enhanced bacterial clearance.Transgenic mice which secreted the amino terminal 71 amino acids of mouse CD14 under the control of al-antitrypsin promoter were produced. The mice were shown to be significantly resistant to systemic lethal Shwartzman reaction.A candidate protein which were implicated in the early cell surface signaling of LPS was selected by pharge display analysis.