Mucus clearance, MyD88-dependent and MyD88-independent immunity modulate lung susceptibility to spontaneous bacterial infection and inflammation.
Mucus clearance, MyD88-dependent and MyD88-independent immunity modulate lung susceptibility to spontaneous bacterial infection and inflammation.
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据推测，粘液淤滞是阻塞性肺疾病发病机制的核心。在Scnn 1b转基因（Scnn 1b-Tg+）小鼠中，上皮Na+通道β亚基的气道靶向过表达导致气道表面脱水，从而导致粘液淤滞和炎症。新生儿Scnn 1b-Tg+小鼠的支气管肺泡灌洗，但不是野生型同窝小鼠，含有增加的粘液，细菌和中性粒细胞，随着年龄的增长而下降。Scnn 1b-Tg+小鼠肺部细菌植物群包括环境和口咽菌种，表明吸入和/或误吸为进入途径。在Scnn 1b-Tg+小鼠中Toll/白细胞介素-1受体衔接分子MyD 88的基因缺失并没有改变气道粘液阻塞，但引起了中性粒细胞募集缺陷和细菌感染增加，并持续到成年期。无菌条件下的Scnn 1b-Tg+小鼠表现出与传统Scnn 1b-Tg+小鼠相似的粘液阻塞和无菌炎症。总的来说，这些数据表明，脱水诱导的粘液淤滞促进感染，复合其他免疫机制的缺陷，并且单独足以引发气道炎症。
It has been postulated that mucus stasis is central to the pathogenesis of obstructive lung diseases. In Scnn1b-transgenic (Scnn1b-Tg+) mice, airway-targeted overexpression of the epithelial Na+ channel β subunit causes airway surface dehydration, which results in mucus stasis and inflammation. Bronchoalveolar lavage from neonatal Scnn1b-Tg+ mice, but not wild-type littermates, contained increased mucus, bacteria, and neutrophils, which declined with age. Scnn1b-Tg+ mice lung bacterial flora included environmental and oropharyngeal species, suggesting inhalation and/or aspiration as routes of entry. Genetic deletion of the Toll/Interleukin-1 receptor adapter molecule MyD88 in Scnn1b-Tg+ mice did not modify airway mucus obstruction, but caused defective neutrophil recruitment and increased bacterial infection, which persisted into adulthood. Scnn1b-Tg+ mice derived into germ-free conditions exhibited mucus obstruction similar to conventional Scnn1b-Tg+ mice and sterile inflammation. Collectively, these data suggest that dehydration-induced mucus stasis promotes infection, compounds defects in other immune mechanisms, and alone is sufficient to trigger airway inflammation.