ROLE OF GLYCOLIPIDS AND LECTINS IN SURFACTANT METABOLISM

肺表面活性剂，用于防止肺动脉塌陷 肺泡，由II型肺泡合成，分泌和回收 上皮细胞表面活性剂的转化机理 II型细胞还不清楚。与纯的混合物相比， 脂质、天然表面活性剂迅速从肺泡腔中清除。的 肺泡腔特有的两种钙依赖性凝集素SP-A和 新发现的SP-D（Spanson等，1989）具有不同的糖结合 特异性，并且两者都是多聚体。我们假设糖脂 存在于表面活性剂中的多价凝集素与多价凝集素相互作用， II型肺泡上皮细胞摄取相关脂质的“把手” 上皮细胞 这两种凝集素在表面活性剂摄取中的作用将被分开 通过利用它们独特的糖结合特异性来设计 并合成二价和三价竞争性抑制剂。这些化合物 将允许在一种凝集素存在的情况下抑制另一种凝集素。 天然糖脂将从表面活性剂和层状糖脂中纯化出来。 体，它们与纯化的凝集素的相互作用将是 表征了在体内， 铁蛋白结合SP-D和SP-A将被证明，以及 选择性抑制剂对其吸收的影响。最后， 天然的和合成的糖脂，连同纯化的凝集素， 在由纯脂质构成的脂质体的摄取中进行评价。

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.