Postnatal development of the lamina reticularis in primate airways

Abstract

The basement membrane zone (BMZ) appears as three component layers: the lamina lucida, lamina densa, and lamina reticularis. The laminas lucida and densa are present during all stages of development. The lamina reticularis appears during postnatal development. Collagens I, III, and V form heterogeneous fibers that account for the thickness of the lamina reticularis. Additionally, there are three proteoglycans considered as integral components of the BMZ: perlecan, collagen XVIII, and bamacan. Perlecan is the predominant heparan sulfate proteoglycan in the airway BMZ. It is responsible for many of the functions attributed to the BMZ, in particular, trafficking of growth factors and cytokines between epithelial and mesenchymal cells. Growth factor binding sites on perlecan include FGF-1, FGF-2, FGF-7, FGF-10, PDGF, HGF, HB-EGF, VEGF, and TGF-beta. Growth factors pass through the BMZ when moving between the epithelial and mesenchymal cell layers. They move by rapid reversible binding with sites on both the heparan sulfate chains and core protein of perlecan. In this manner, perlecan regulates movement of growth factors between tissues. Another function of the BMZ is storage and regulation of FGF-2. FGF-2 has been shown to be involved with normal growth and thickening of the BMZ. Thickening of the BMZ is a feature of airway remodeling in asthma. It may have a positive effect by protecting against airway narrowing and air trapping. Conversely, it may have a negative effect by influencing trafficking of growth factors in the epithelial mesenchymal trophic unit. However, currently the significance of BMZ thickening is not known.