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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL032109-06
Application #
3343361
Study Section
Human Embryology and Development Subcommittee 2 (HED)
Project Start
1984-04-01
Project End
1991-06-30
Budget Start
1989-07-01
Budget End
1991-06-30
Support Year
6
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of Miami School of Medicine
Department
Type
Schools of Medicine
DUNS #
City
Miami
State
FL
Country
United States
Zip Code
33101
Whitney, P L; Starcher, B; Brittain, C (1992) Soluble beta-galactoside specific lectin is developmentally regulated in lungs of neonatal black mice and beige mice. Exp Lung Res 18:553-61
Iqbal, J; Whitney, P (1991) Use of cyanide and diethyldithiocarbamate in the assay of superoxide dismutases. Free Radic Biol Med 10:69-77
Clerch, L B; Whitney, P; Massaro, D (1989) Rat lung lectin gene expression is regulated developmentally and by dexamethasone. Am J Physiol 256:C501-5
Clerch, L B; Whitney, P; Hass, M et al. (1988) Sequence of a full-length cDNA for rat lung beta-galactoside-binding protein: primary and secondary structure of the lectin. Biochemistry 27:692-9
Clerch, L B; Whitney, P L; Massaro, D (1987) Rat lung lectin synthesis, degradation and activation. Developmental regulation and modulation by dexamethasone. Biochem J 245:683-90
Whitney, P L; Powell, J T; Sanford, G L (1986) Oxidation and chemical modification of lung beta-galactoside-specific lectin. Biochem J 238:683-9
Whitney, P; Maxwell, S; Ryan, U et al. (1985) Synthesis and binding of lactose-specific lectin by isolated lung cells. Am J Physiol 248:C258-64