Our long range goal is to increase knowledge of the neonatal development of the gas-exchange region of the lung. Our more immediate goal is to characterize the structure, function and regulation of a dimeric soluble, B-galactoside-specific lectin (designated lectin-14K based on its approximate subunit molecular weight) that is found in the lung of several species including rat and man. In rat, hamster and guinea pig lungs the lectin activity peaks at the same time that the lung is undergoing a period of intense alveolar development. We have determined the sequence of 21 amino acids in lectin-14K and used this information to synthesize an oligonucleotide probe that we will use to identify and isolate the cDNA for lectin-14K. The lectin cDNA will be used to determine nucleotide and amino acid sequences and to study the developmental and hormonal regulation of lectin gene transcription and mRNA translation. We will also characterize lectin-17K and lectin-32K, two monomeric lectins with sugar specificities that are very similar to lectin-14K and could, therefore, compete for the same receptors. Finally, we will study lectin synthesis, turnover, and secretion in cultured lung cells with the aim of characterizing the mechanisms that regulate lectin secretion and its extracellular function. We think the key issues and importance of our work may be narrowed to the following: 1) we will substantially augment the very little information tht exists on the developmental regulation of expression of the lectin-14K gene, and 2) we may elucidate the role of the lectin in the architectural development of the gas-exchange region of the lung and possibly of the lung's arterioles. We hope to achieve our goals using techniques of cell physiology and cell and molecular biology to understand this aspect of lung development. We think our studies will provide important information on the molecular and cellular basis of lung development and may provide a basis for understanding developmental defects of the lung.
