Content and synthesis of glycosaminoglycans in the developing lung.

Abstract

A B S T R A C T The function of lung is fundamentally linked to the connective tissue composition of the alveolar interstitium. The composition and synthesis of one class of interstitial connective tissue components, the glycosaminoglycans (GAG), was determined in lung parenchyma of rabbits at different stages of development. Parenchymal GAG content ranged between 0.2 and 0.4% (wt/wt) of dry weight, with highest concentration in adult lung. There were significant changes in types of GAG present at different ages. Fetal lungs contained a relatively high proportion of chondroitin 4-sulfate while the GAG in lung parenchyma of older animals was predominantly dermatan sulfate, heparan sulfate, and heparin. Methods were developed for the study of rates of synthesis of GAG by incorporation of [1-'4C]glucosamine into lung explants. The rate of synthesis of total GAG per cell increased with development to a maximum in lung from weanling rabbits and fell to low rates of synthesis in mature rabbits. Fetal rabbit lung parenchyma synthesized mostly hyaluronic acid and heparan sulfate, while in weanling rabbit parenchyma hyaluronic acid and chondroitin 4/6-sulfate synthesis was greatest. In mature animals, the rates of synthesis of all types of GAG were relatively low structure, determination of lung mechanical properties, interchange of nutrients and metabolites between the capillary and epithelial cells, and diffusion of 02 and C02 between the alveolar gas and the blood. The two major constituents of interstitial connective tissue, collagen and elastin, comprise more than 90% of the noncellular interstitial dry weight. The remainder has been termed the "amorphous ground substance" (1, 2).The term "amorphous" is used because this material is poorly defined morphologically. It is known to include serum proteins, glycoproteins, cellular metabolites, small solutes (,e.g., glucose, urea, salts), and proteoglycans (3). The latter are macromolecules composed of a protein backbone with multiple, large polysaccharide side chains termed glycosaminoglycans (GAG) 1 (4). The GAG also include hyaluronic acid, which may not be part of a protein-polysaccharide complex. In tissues other than lung and in simplified model systems with purified components, it has been shown that specific types of GAG will: (a) associate with other connective tissue elements (5, 6); (b) influence the rate of synthesis of connective tissue components (7, 8); (c) affect the hydration of connective tissue (9); and (d) influence the rate of collagen fibril formation and subsequent stability of these fibrils (5, 10). Thus, the quantity and type of GAG in the lung interstitium may have significant effects on the mechanical properties of the lung as well as on gas, solute, and fluid movements between the alveolar space and capillary (11). It is the purpose of this study to describe methods to quantitate the composition and synthesis of GAG in the lung interstitium and to define the normal pattern of GAG accumulation and synthesis in the growing lung. METHODSMaterial...

Lcl of Legionella pneumophila Is an Immunogenic GAG Binding Adhesin That Promotes Interactions with Lung Epithelial Cells and Plays a Crucial Role in Biofilm Formation

“…In addition to heparin, we show that rLcl binds to highly sulfated GAG analogs like chondroitin sulfate A, which is a major component of lung polysaccharides (37,71). Although the rLcl protein was eluted from a heparin (5 to 30 kDa) chromatography column at 500 mM NaCl, ELISA binding assay values with heparin (4 to 6 kDa) were relatively low compared to those of other GAGs.…”

Metabolic Activity of Developing Rabbit Lung

“…It is for this reason that most of the interest in lung metabolism during the perinatal period has been focused on surfactant synthesis and secretion (13,14,20,28). With the exception of collagen (3) and glycosaminoglycan synthesis (18), very little is known on other aspects of lung metabolism during this period of rapid lung growth; in addition, there are only few systematic studies that extend throughout the developmental period into adulthood and old age. In the present study, we have investigated glucose metabolism and lipid and protein synthesis in rabbit lung from 3 days before birth to 2 years of age.…”

Elastin and Collagen in the Fetal Sheep Lung. II. Relationship to Mechanical Properties of the Lung

“…predominate ( I . [3][4][5][6][7][8][9][10][11][12][13][14][15]. In one of these stuciiCs a slight decrease in the elastin to collage11 ratio of' t t~c fctal rnor1l\c!…”