Reduction of collagen VII anchoring fibrils in the airway basement membrane zone of infant rhesus monkeys exposed to house dust mite

Abstract

Collagen VII anchoring fibrils in the basement membrane zone (BMZ) are part of a supracellular anchoring network that attaches the epithelium to the BMZ. Sloughing of airway epithelium in asthmatics (creola bodies) is a pathology associated with the supracellular anchoring network. In a rhesus monkey model of house dust mite (HDM)-induced allergic asthma, we found increased deposition of collagen I in the BMZ. In this study, we determine whether HDM also affected deposition of collagen VII in the BMZ. In the developing airway of rhesus monkeys, the width of collagen VII anchoring fibrils in the BMZ was 0.02 +/- 0.04 microm at 1 mo of age. At 6 mo the width had increased to 1.28 +/- 0.34 microm and at 12 mo 2.15 +/- 0.13 microm. In animals treated with HDM, we found a 42.2% reduction in the width of collagen VII layer in the BMZ at 6 mo (0.74 +/- 0.15 microm; P < 0.05). During recovery, the rate of collagen VII deposition returned to normal. However, the amount of collagen VII lost was not recovered after 6 mo. We concluded that normal development of the collagen VII attachment between the epithelium and BMZ occurs in coordination with development of the BMZ. However, in HDM-treated animals, the collagen VII attachment with the epithelium was significantly reduced. Such a reduction in collagen VII may weaken the supracellular anchoring network and be associated with sloughing of the epithelium and formation of creola bodies in asthmatics.

Fig. 1.

Illustration of the supracellular anchoring system connecting the epithelium with the basement membrane zone (BMZ) and the ECM. Intermediate filaments of columnar and basal cells are connected together with desmosomes. Intermediate filaments of basal cells [cytokeratins (CK) 5 and 14] connected to desmosomes are also attached to hemidesmosomes. Hemidesmosomes are attached to the lamina (l.) densa by laminin 5. Collagen VII anchoring fibrils attach to laminin 5 in the l. densa, and collagen I fibers in the l. reticularis. The l. reticularis is attached to the ECM by oxytalan fibers of the elastic lamina.

Fig. 2.

Light micrograph of the tracheal epithelium in a 3-mo-old animal. The average height of the epithelium increases as the animals get older. The increases in average height correlates with the increase in the circumference of the trachea in the growing animals up to 12 mo (Table 1). The BMZ is not distinct in standard light microscope preparations stained with hematoxylin and eosin. It is marked with arrowheads. Bar: 10 μm.

Fig. 3.

Immunohistochemistry of the collagen I in a 3-mo-old animal demonstrating the density and width of the BMZ (arrowheads). The width of the BMZ is related to its role in attaching the epithelium with the ECM. Collagen VII is found in the epithelial surface of the BMZ. Bar: 10 μm.

Fig. 4.

Immunohistochemistry of the collagen VII layer of anchoring fibrils on the epithelial interface of the BMZ in a 3-mo-old animal (arrowheads). Preparations such as this were used to measure the width of the collagen VII layer. Bar: 10 μm.

Fig. 5.

Comparing the filtered air (FA) and house dust mite (HDM) groups shows that during recovery the rate of collagen VII anchoring fibril growth returned to normal in the HDM group. However, the collagen VII layer was still significantly less than the FA group. Compared with the absolute change in width of the collagen VII layer, there was an initial decrease of 0.54 μm at 6 mo on the HDM protocol. After recovery in FA for 6 mo, the difference in width collagen VII layer was 0.47 μm, indicating that the amount of collagen VII lost during the HDM protocol had not been replaced.