Departments of Microbial and Molecular Pathogenesis and Medicine, College of Medicine and Clinical Science and Translational Research Institute, Texas A&M Health Science Center, 2121 West Holcombe Boulevard, Houston, TX 77030, USA.
Curr Allergy Asthma Rep. 2010 Sep;10(5):320-5. doi: 10.1007/s11882-010-0134-y.
Pulmonary alveolar proteinosis (PAP) is a rare disease of the lung characterized by the accumulation of surfactant-derived lipoproteins within pulmonary alveolar macrophages and alveoli, resulting in respiratory insufficiency and increased infections. The disease is caused by a disruption in surfactant catabolism by alveolar macrophages due to loss of functional granulocyte-macrophage colony-stimulating factor (GM-CSF) signaling. The underlying molecular mechanisms causing deficiencies in GM-CSF signaling are as follows: 1) high levels of neutralizing GM-CSF autoantibodies observed in autoimmune PAP; 2) mutations in CSF2RA, the gene encoding the alpha chain of the GM-CSF receptor, observed in hereditary PAP; and 3) reduced numbers and function of alveolar macrophages as a result of other clinical diseases seen in secondary PAP. Recent studies investigating the biology of GM-CSF have revealed that not only does this cytokine have an indispensable role in lung physiology, but it is also a critical regulator of innate immunity and lung host defense.
肺泡蛋白沉积症（PAP）是一种罕见的肺部疾病，其特征是肺泡巨噬细胞和肺泡内的表面活性剂衍生脂蛋白蓄积，导致呼吸功能不全和感染增加。该疾病是由于肺泡巨噬细胞中表面活性剂代谢的破坏，导致功能丧失的粒细胞-巨噬细胞集落刺激因子（GM-CSF）信号。导致 GM-CSF 信号转导缺陷的潜在分子机制如下：1）在自身免疫性 PAP 中观察到高水平的中和 GM-CSF 自身抗体；2）在遗传性 PAP 中观察到编码 GM-CSF 受体α链的 CSF2RA 基因突变；3）由于继发性 PAP 中出现的其他临床疾病，导致肺泡巨噬细胞数量和功能减少。最近对 GM-CSF 生物学的研究表明，这种细胞因子不仅在肺生理学中具有不可或缺的作用，而且还是先天免疫和肺宿主防御的关键调节剂。
