Lemjabbar Hassan, Basbaum Carol
Biomedical Sciences Program, Cardiovascular Research Institute and Department of Anatomy, University of California, San Francisco, California, USA.
Nat Med. 2002 Jan;8(1):41-6. doi: 10.1038/nm0102-41.
In the lungs of cystic fibrosis patients, overproduction of mucus leads to morbidity and mortality by obstructing airflow and shielding bacteria from antibiotics. Here we demonstrate that overproduction of mucus is a direct result of the activation of mucin gene expression by Gram-positive bacteria. Bacterial lipoteichoic acid activates the platelet-activating factor receptor, which is G protein-coupled. This results in activation of a disintegrin and metalloproteinase (ADAM10), kuzbanian, cleavage of pro heparin-binding epidermal growth factor and activation of the epidermal growth factor receptor. Unlike responses in macrophages, the epithelial-cell response to lipoteichoic acid does not require Toll-like receptor 2 or 4.
在囊性纤维化患者的肺部,黏液过度产生会阻碍气流并使细菌免受抗生素作用,从而导致发病和死亡。在此我们证明,黏液过度产生是革兰氏阳性菌激活黏蛋白基因表达的直接结果。细菌脂磷壁酸激活血小板活化因子受体,该受体是G蛋白偶联受体。这导致解整合素和金属蛋白酶(ADAM10)、库兹班蛋白激活,前肝素结合表皮生长因子裂解以及表皮生长因子受体激活。与巨噬细胞中的反应不同,上皮细胞对脂磷壁酸的反应不需要Toll样受体2或4。