Analysis of endotoxin antagonism of lipoteichoic acids from oral streptococci

1. 口腔链球菌、血链球菌和变形链球菌的脂磷壁酸 (LTA) 可拮抗 CD14 阳性人牙龈成纤维细胞 (HGF) 和人单核细胞响应内毒素（LPS、脂多糖）及其活性部分、合成脂质 A.2 产生炎症细胞因子的活性。除了 CD14 作为细菌成分受体外，Toll 样受体 (TLR) 还将这些成分的信号转导到细胞中。使用基因敲除小鼠，其他细菌的 LTA 和 LPS 分别以 CD14/TLR2 和 CD14/TLR4 依赖性途径激活小鼠巨噬细胞。 3．一种众所周知的LPS拮抗剂，合成的脂质A前体(LA-14-PP)抑制人体系统中CD14/TLR4配体(LPS)以及CD14/TLR2配体(LTA)的功能，表明CD14在拮抗作用中发挥着重要作用。4．抗CD14抗体抑制口腔链球菌LTA与人单核细胞的结合，并且在天然聚丙烯酰胺凝胶电泳中LTA与重组CD14结合，表明LTA的拮抗作用是通过与细胞表面CD14.5竞争来介导的。牙周致病性牙龈卟啉单胞菌半胱氨酸蛋白酶（gingipain）和人中性粒细胞丝氨酸蛋白酶（弹性蛋白酶）优先水解人单核细胞和 HGF 上的 CD14，导致细胞的 LPS 反应性下调。

1. Lipoteichoic acids (LTAs) of oral streptococci, Streptococcus sanguis and Streptococcus mutans, was shown to antagonize the activity of inflammatory cytokine production from CD14-positive human gingival fibroblasts (HGF) and human monocytes in response to endotoxin (LPS, lipopolysaccharide) and its active moiety, synthetic lipid A.2. In addition to CD14 as a bacterial component receptor, Toll-like receptors (TLRs) transduce signals of the components into the cells. LTAs of other bacteria and LPS activated murine macrophages in a CD14/TLR2-and CD14/TLR4-dependent pathway, respectively, using gene knockout mice.3. An well known LPS antagonist, a synthetic lipid A precursor (LA-14-PP) inhibited the function of CD14/TLR4 ligand (LPS) as well as CD14/TLR2 ligand (LTA) in human system, suggesting that CD14 is critically involved in the antagonism.4. Binding of oral streptococcal LTAs to human monocytes was inhibited by anti-CD14 antibody and the LTAs binded to recombinant CD14 in a native-polyacrylamide gel electrophoresis, showing that the antagonism of the LTAs is mediated by competing with cell surface CD14.5. Periodontal pathogenic Porphyromonas gingivalis cysteine proteinase (gingipain) and human neutrophil serine proteinase (elastase) preferentially proteolysed CD14 on human monocytes and HGF, resulting in down-modulation of LPS responsiveness of the cells.