Attachment of columnar airway epithelial cells in asthma
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.
Section snippets
Human samples
Bronchial biopsy specimens were taken from five healthy adults and five patients with atopic asthma. The study was conducted in accordance with the declaration of Helsinki and was approved by the Ethics Committee at the Faculty of Medicine at the University of Uppsala.
Rat trachea
Fig. 1 shows the complete epithelium section in the rat. The rat airway epithelium is less high than the human airway epithelium, and the basal cells are less in number and smaller in size compared to humans (cf. Fig. 5). The percentage of basal lamina covered by columnar cells was much higher in the rats (Fig. 1). At higher magnifications desmosome attachments between columnar and basal cells (Fig. 2), as well as between basal cells were observed. The desmosomes in the rat tracheas seemed to
Discussion
The structure of the respiratory epithelium in a number of animal species was investigated quantitatively by Evans et al. (1989), but no data on human epithelium were included. The measurements on rat respiratory epithelium in the present study were carried out to see whether our methods of determining quantitative parameters agreed with those of Evans et al. (1989). This is indeed the case. In the rat, for the columnar cell height values ranging from 11.5 to 16 μm were found by Evans et al.
Acknowledgements
The technical assistance of Anders Ahlander, Marianne Ljungkvist, and Leif Ljung is gratefully acknowledged. This study was financially supported by the Swedish Asthma and Allergy Foundation, the Swedish Science Research Council, and the Swedish Heart-Lung Foundation.
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- 1
The BHR group consists of Kawa Amin (Department of Medical Cell Biology), Anders Ahlander (Department of Medical Cell Biology), Eythór Björnsson (Section of Lung Medicine and Allergology), Gunnar Boman (Section of Lung Medicine and Allergology), Britt-Martie Eriksson (Section of Infectious Diseases), Björn Gudbjörnsson (Section of Rheumatology), Monika Hall (Section of Clinical Physiology), Göran Hedenstierna (Section of Clinical Physiology), Hans Hedenström (Section of Clinical Physiology), Lena Håkansson (Laboratory for Inflammation Research, Department of Medicine, Uppsala University), Marieann Högman (Department of Medical Cell Biology), Christer Jansson (Section of Lung Medicine and Allergology), Maria Lempinen (Laboratory for Inflammation Research, Department of Medicine, Uppsala University), Kerstin Lindblad (Laboratory for Inflammation Research, Department of Medicine, Uppsala University), Dóra Lúdviksdóttir (Section of Lung Medicine and Allergology), Otto Nettelbladt (Section of Lung Medicine and Allergology), Godfried M. Roomans (Department of Medical Cell Biology), Lahja Sevéus (Pharmacia & Upjohn Diagnostics, Uppsala, Sweden), Ulrike Spetz-Nyström (Section of Lung Medicine and Allergology), Gunnemar Stålenheim (Section of Lung Medicine and Allergology), Sigrídur Valtysdottír (Section of Rheumatology), Charlotte Woschnagg (Laboratory for Inflammation Research, Department of Medicine, Uppsala University), Per Venge (Laboratory for Inflammation Research, Department of Medicine, Uppsala University).