ROLE OF GLYCOLIPIDS AND LECTINS IN SURFACTANT METABOLISM

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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.