CYTODYNAMICS OF IN-VITRO DEVELOPING AIRWAYS AND INTERACTION WITH EXTRACELLULAR-MATRIX PROTEINS

We studied epithelial and mesenchymal cell kinetics during lung branch ing and the possible importance of proteoglycan and collagen in rat fe tal organ culture for 5 days, starting from 15 days gestation, The lun gs were randomly divided into three groups: (1) basal medium (controls ); (2) basal medium + beta-D-xyloside (beta-XYL); and (3) basal medium + cis-4-hydroxy-L-proline (cis-HYP), The labeling index of incorporat ion of 5-bromo-2-deoxyuridine (BrdU) was used as an indicator of DNA s ynthesis and assessed in the parent airways and in the tips and sides of peripheral buds. In controls, BrdU incorporation was highest in bud tips, followed by bud sides and then parent airway for both epitheliu m and mesenchyme. These data suggest that preferential cell proliferat ion occurs in normal airway branching, In parent airways, labeling of epithelium and mesenchyme was consistently diminished throughout the c ulture period in beta-XYL, whereas in cis-HYP this was not the case. I n the peripheral buds, the DNA synthetic activity in both epithelium a nd mesenchyme was impaired in beta-XYL and cis-HYP, but the effect was more marked in beta-XYL, We conclude that although collagen may be re quired in peripheral bud morphogenesis, the proteoolycans appear to be essential in growth and development of both parent airways and periph eral buds in the lung.