Attachment of columnar airway epithelial cells in asthma

Abstract

Shedding of airway epithelial cells is a common finding in asthma. In this study, the attachment of the airway epithelial cells to the basal lamina (BL) was investigated by transmission electron microscopy (TEM) of biopsies from patients with atopic asthma and healthy controls. The following parameters were quantitatively determined: the height of the epithelium and of the columnar cells, the number of basal cells per 100 μm of basal lamina, the contact surfaces of basal cells or columnar cells with the basal lamina, and between basal cells and columnar cells. In order to compare the quantitative method with previous literature data, measurements were also carried out on rat airway epithelium. Compared to the rat, the columnar cell height in the human is increased, basal cells are smaller, and there is a larger contact area between basal cells and basal lamina, as well as between basal and columnar cells. The contact area between columnar cells and basal lamina is hence less in the human airway. The contact area between columnar cells and basal lamina in asthmatics is significantly less than in healthy controls, due to larger intercellular spaces. It is concluded that attachment of columnar cells to the basal lamina occurs mainly indirectly, via desmosomal attachment to basal cells, and that direct attachment of columnar cells to the basal lamina is weakened in asthmatics.

Introduction

Light and electron microscopic studies of bronchial biopsies in asthma have added valuable information to that obtained from studies of lungs taken at necropsy. In particular, mucosal biopsies taken during bronchoscopy have highlighted the early damage to the surface epithelium in atopic asthma, even of mild severity (reviewed in Jeffery et al., 1992, Knight and Holgate, 2003). In severe asthma bronchial epithelial cells are damaged and detached, which may be related to the bronchial hyperresponsiveness (BHR) that characterizes asthma (Laitinen et al., 1985, Lozewicz et al., 1990, Benayoun et al., 2003). Epithelial shedding is characteristic of bronchial asthma. Bronchial washings reveal that epithelial cells are shed in clusters composed entirely of columnar cells, and asthma patients have an increased number of epithelial cell clumps (creola bodies) in their sputum (Woltmann et al., 1999). According to electron microscopy the basal cells remain attached to the basal lamina (BL). The mechanism of epithelial shedding is not clear. In asthma, there may be a primary defect in the epithelium, which leads it to respond abnormally to various stimuli and also prevents it from proceeding towards a normal repair process (reviewed in Holgate, 2000). It has been hypothesized that airway hyperreactivity in asthma may be related to epithelial desquamation through mechanisms involving loss of epithelium-derived relaxing factor (Fahy, 2001). Some studies have shown that shedding of the columnar epithelial cells starts in the middle of the epithelium, where the columnar epithelial cells are still attached to each other at the luminal side, but separated from the basal cells by oedema fluid (reviewed in Laitinen and Laitinen, 1994).

In a recent ultrastructural study in our laboratory, it was found that in the airway epithelium of asthma patients, desmosomal contacts between epithelial cells were reduced (Shahana et al., 2003). Also experimental studies have pointed to a possible role of desmosomes in epithelial shedding. Poly-l-arginine, a functional analogue of the eosinophil granule derived major basic protein (MBP), which is elevated in the serum of asthma patients, caused a reduction in desmosomes in cultured human bronchial epithelial cells (Shahana et al., 2002).

Another aspect of interest is the attachment of the epithelial cells to the basal lamina. Studies in animals have shown that basal cells form hemidesmosome attachments with the basal lamina and desmosome attachments with adjacent cells (reviewed in Laitinen and Laitinen, 1994). A quantitative study comparing cell attachment in the airway epithelium has been carried out for a number of animal species (Plopper et al., 1980, Evans et al., 1989, Evans et al., 1990) but not for humans. In the present study, we carried out quantitative measurements of the attachment of airway epithelial cells in healthy humans and patients with atopic asthma. In order to be able to compare our quantitative results with those of Evans et al. (1989), we included the rat in our study.