ROLE OF GLYCOLIPIDS AND LECTINS IN SURFACTANT METABOLISM

肺表面活性物质，防止肺萎陷所需 肺泡是由II型肺泡合成、分泌和再循环的 上皮细胞。表面活性物质周转的控制机制 II型细胞尚不清楚。与纯净的混合物相比 脂类，天然的表面活性物质，被迅速从牙槽腔中去除。这个 肺泡腔特有的两种钙依赖凝集素：SP-A和 新发现的SP-D(Persson等人)，具有明显的糖结 特殊性，并且两者都是多聚体。我们假设糖脂 存在于表面活性剂中，与多价凝集素相互作用，并提供 II型肺泡摄取相关脂类的“柄” 上皮细胞。 这两种凝集素在表面活性物质吸收中的作用将被分开。 通过利用它们独特的糖结合特性来设计 合成二价和三价竞争性抑制剂。这些化合物 将允许在一个凝集素存在另一个凝集素的情况下抑制另一个凝集素。 天然糖脂将从表面活性剂和片状糖脂中提纯 它们与纯化的凝集素的相互作用将是 特色化的。体内摄取阿司匹林的轨迹和动力学 将演示铁蛋白偶联的SP-D和SP-A，以及 选择性抑制剂对其摄取的影响。最后一点是， 天然和合成的糖脂，连同纯化的凝集素，将 在由纯脂组成的脂质体的摄取方面进行评价。

Pulmonary surfactant, required to prevent collapse of the pulmonary alveolus, is synthesized, secreted, and recycled by the type II alveolar epithelial cell. The mechanisms controlling the turnover of surfactant by the type II cell are not yet understood. As compared with mixtures of pure lipids, native surfactant is rapidly removed from the alveolar space. The two calcium-dependent lectins unique to the alveolar space, SP-A and the newly discovered SP-D (Persson et al. 1989), have distinct sugar-binding specificities, and are both multimeric. We hypothesize that glycolipids present in surfactant interact with the multivalent lectins and provide a "handle" for the uptake of associated lipids by the type II alveolar epithelial cell. The roles of the two lectins in the uptake of surfactant will be separated by employing their distinctive saccharide-binding specificities to design and synthesize di- and trivalent competitive inhibitors. These compounds will permit the inhibition of one lectin in the presence of the other. Native glycolipids will be purified from both surfactant and lamellar bodies, and their interactions with the purified lectins will be characterized. In vivo, the locus and kinetics of uptake of ferritin-conjugated SP-D and SP-A will be demonstrated, as well as the effect of the selective inhibitors on their uptake. Finally, the role of natural and synthetic glycolipids, together with the purified lectins, will be evaluated in the uptake of liposomes constituted from pure lipids.