Alterations in Alveolar Basement Postnatal Lung Growth

We studied the ultrastructural characteristics of alveolar basement membranes (ABM) and capillary basement membranes (CBM) in rat lungs at birth, at 8-10 d of age, during alveolar formation, and at 6-10 wk of age, after most alveoli have formed. We also measured in vitro lung proteoglycan and heparan sulfate synthesis at each age. We noted three major age-related changes in pulmonary basement membranes. (a) Discontinuities in the ABM through which basilar cytoplasmic foot processes extend are present beneath alveolar type-2 cells but not alveolar type-1 cells. These discontinuities are most prevalent at birth but also exist in the adult. (b) Discontinuities are also present in CBM at the two earliest time points but are maximal at 8 d of age rather than at birth. Fusions between ABM and CBM are often absent at 8 d of age, but CBM and CSM/ABM fusions were complete in the adult. (c) Heparan sulfate proteoglycans identified with ruthenium red and selective enzyme degradation are distributed equally on epithelial and interstitial sides of the ABM lamina densa at birth, but decrease on the interstitial side with age. In vitro proteoglycan and heparan sulfate accumulation at birth was two times that at 8 d and five times tha: in the adult. Discontinuities in ABM allow epithelial-mesenchymal interactions that may influence type-2 cells cytodifferentiation. Discontinuities in CBM suggest that capillary proliferation and neovascularization are associated with alveolar formation at 8 d. When CBM becomes complete and forms junctions with ABM, lung neovascularization likely ends as does the ability to form new alveoli. The lung parenchyma of most mammalian species contains few recognizable gas exchange units (alveoli) at birth (1). The majority of alveoli develop postnatally in a short period of time ranging from days in small rodents to years in man (1, 2). After this intense period of restructuring of the gas exchange surface of the lung, few new alveoli form under normal circumstances. Furthermore, once this period of postnatal morphogenesis has passed, the mature lung appears incapable of forming large numbers of new alveoli in response to growth stimuli such as pneumonectomy (3). Thus the circumstances associated with formation of lung gas exchange units appear to be unique and limited to a relatively short period of postnatal life. Basement membranes have been shown to play an important role in regulating tissue morphogenesis in a number of organs (4). Much of this role involves regulation of the interface between epithelium and mesenchyme and regulation of proliferation and differentiation of key cells in the morphogenic process. Basement membranes also compartmentalize tissues, thus contributing to their structural organization. These basement membrane developmental functions have been demonstrated in tissues as diverse as cornea (5), tooth (6), and kidney (7, 8), and in branching organs such as salivary and mammary gland (9-11). Branching morphogenesis of the bronchial tree in fetal life also seems to involve interaction of epithelium and mesenchyme, most likely regulated by airway basement membranes (12-15). However, little information exists relating to the role that basement membranes might play in development of the gas exchange surfaces of the lung during postnatal life. Because the process of postnatal alveolar formation involves tissue compartmentalization, cell proliferation and differentiation, and most probably epithelial-mesenchymal interactions, it seems likely that components of basement membranes would be important determinants of postnatal alveolarization. We have therefore applied methods for highlighting basement membrane components previously used by us for defining the ultrastructure of alveolar wall basement membranes in the adult rat (16, 17) to define changes that occur in basement membranes during postnatal formation of alveoli. We have TUE IOURNAL OF CELL BIOLOGY -VOLUME 95 NOVEMBEr 1982 394-402 394 © The Rockefeller University Press . 0021-9525/82/11/0394/09 $1.00 on May 3, 2019 jcb.rupress.org Downloaded from http://doi.org/10.1083/jcb.95.2.394 Published Online: 1 November, 1982 | Supp Info: