deMello D E, Heyman S, Phelps D S, Floros J
Department of Pathology, Cardinal Glennon Children's Hospital, St. Louis, MO 63104.
Am J Pathol. 1993 May;142(5):1631-40.
Prematurely born infants can develop the neonatal respiratory distress syndrome (RDS) because of a deficiency of pulmonary surfactant. This lipoprotein complex synthesized by type II pneumocytes has different ultrastructural forms--intra- and extracellular lamellar bodies, which within the alveoli are transformed into tubular myelin, and this in turn gives rise to the surface monolayer, the functionally active form of surfactant. We have previously shown that at autopsy RDS lungs lack tubular myelin and have decreased immunoreactivity for antisera to surfactant protein A (SP-A), an important component of tubular myelin. Therefore, we proposed a role for SP-A in the conversion of lamellar bodies to tubular myelin and in the pathogenesis of RDS. To explore this possibility further, we compared in 14 RDS and 14 control lungs the distribution of SP-A in ultrathin sections, using affinity-purified rabbit anti-human-SP-A IgG and goat anti-rabbit IgG-conjugated with 10 nm colloidal gold particles. In controls, gold label was present in lamellar bodies, endoplasmic reticulum, on the cytoplasmic membrane of type II cells, and on lamellar bodies and tubular myelin either within alveoli or macrophages. In RDS lungs, reduced label was present in the same intracellular compartments and organelles, except in tubular myelin, which is absent. It is postulated that if SP-A is indeed necessary for the conversion of lamellar bodies to tubular myelin, in RDS either there is a deficiency of adequate amounts of functional SP-A or some other important component of surfactant is missing.
早产婴儿可能会因肺表面活性物质缺乏而患上新生儿呼吸窘迫综合征(RDS)。这种由II型肺细胞合成的脂蛋白复合物具有不同的超微结构形式——细胞内和细胞外板层小体,在肺泡内它们会转化为管状髓磷脂,而管状髓磷脂又会进而形成表面单分子层,即表面活性物质的功能活性形式。我们之前已经表明,在尸检时RDS肺缺乏管状髓磷脂,并且对作为管状髓磷脂重要成分的表面活性物质蛋白A(SP-A)抗血清的免疫反应性降低。因此,我们提出SP-A在板层小体向管状髓磷脂的转化以及RDS的发病机制中发挥作用。为了进一步探究这种可能性,我们使用亲和纯化的兔抗人SP-A IgG和与10纳米胶体金颗粒偶联的山羊抗兔IgG,比较了14例RDS肺和14例对照肺超薄切片中SP-A的分布。在对照中,金标记出现在板层小体、内质网、II型细胞的细胞质膜上,以及肺泡内或巨噬细胞内的板层小体和管状髓磷脂上。在RDS肺中,相同的细胞内区室和细胞器中标记减少,但管状髓磷脂中没有(因为RDS肺中不存在管状髓磷脂)。据推测,如果SP-A确实是板层小体转化为管状髓磷脂所必需的,那么在RDS中,要么是功能性SP-A的量不足,要么是表面活性物质的其他一些重要成分缺失。