Lung collagen heterogeneity. Synthesis of type I and type III collagen by rabbit and human lung cells in culture

Abstract

The fetal and adult lung have a constant level of collagen synthesis that represents 4-5% of the total amino acids incorporated into lung protein. Prior studies have demonstrated that this collagen is not homogeneous but rather is composed of at least two collagen types, I and II, each localized to specific lung structures. Although it is known that explants of rabit lung parenchyma and blood vessels synthesize type I collagen and that rabbit lung tracheobronchial tree synthesizes type II collagen, it has been suggested that other collagen types are present in lung. It is not known which cells are responsible for the synthesis of any lung collagen type. To approach the problem of additional lung collagen heterogeneity and the identification of the cells responsible for lung collagen synthesis, techniques were developed to examine collagen synthesized by lung cells in culture. 10-15% of the proteins synthesized by confluent cultures of rabbit lung cells and fetal human lung fibroblasts are collagen. Separation and purification of this collagen by ion-exchange chromatography and cyanogen bromide (CNBr) peptide mapping techniques indicate that collagen secreted by these cells is composed of two collagen types, I and III. The CNBr peptides of type I collagen secreted by these cells are identical to the CNBr peptides of type I collagen synthesized by lung parenchyma and blood vessels. The peptides of type III collagen secreted by these cells are identical to fetal skin type III collagen CNBr peptides. The existence of 40 cell types and the insolubility of lung collagen increase the complexity of identifying the types of collagen in lung and the cells responsible for the synthesis of each type. The techniques described here should eventually lead to a complete description of the synthesis and composition of lung collagen, thus providing a probe to understand the role of collagen in lung development and structure in health and disease.