Although significant development occurs in the lung after birth, investigations of postnatal lung development have not received the attention that fetal lung development has enjoyed. Development of both the lung alveoli and vasculature occurs during the postnatal period for the rat, as with several mammalian species. The activity of a beta-galactoside specific lectin (galaptin) is maximal in the lung at the time that these developmental changes are taking place. The function of galaptin is unknown, although it appears to have a predominantly intracellular localization. Studies are proposed that will investigate the hormonal regulation of galaptin production by the lung and by cultured pulmonary and vascular cells. Rat pups will be examined at various times during the early postnatal period for the alteration in galaptin synthesis and degradation by dexamethasone, thyroxine, and insulin, using lung slices. Studies of galaptin synthesis and degradation will also be done using organ cultures established from postnatal lung tissues. These organ cultures will allow direct effects of hormones to be measured. Similar studies will be done using cultured cells. The binding and internalization of galaptin by cultured cells will be investigated and kinetic rate constants and number of binding sites per cell calculated. Studies are also proposed that will investigate the effects of galaptin on the motility, metabolism, DNA and protein synthesis, and regulation of enzymatic activities of cultured cells. Pulmonary fibroblasts, macrophages, and endothelial cells, as well as vascular smooth muscle and endothelial cells, will be used in these studies. An investigation of the effects of galaptin on the synthesis of elastin by lung organ cultures and cultured vascular cells will also be done. These studies will lead to the understanding of the factors which regulate the appearance of galaptin in the lung. Further, the possible cellular and biochemical effects of galaptin on pulmonary and vascular cells will begin to be defined. The long term objectives of this research are: (a) to elucidate the role(s) of galaptin in lung development and in the adult lung, (b) to determine the factors that play a role in the regulation of postnatal lung development, and (c) to establish organ and cell cultures that will be useful in further research on the regulation of galaptin activity and function.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
1R29HL038944-01
Application #
3471438
Study Section
Human Embryology and Development Subcommittee 2 (HED)
Project Start
1987-08-01
Project End
1992-07-31
Budget Start
1987-08-01
Budget End
1988-07-31
Support Year
1
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Morehouse School of Medicine
Department
Type
Schools of Medicine
DUNS #
City
Atlanta
State
GA
Country
United States
Zip Code
30310