Mast cells and neuropeptides in the rat laryngeal mucosa : Edema formation and effects of irradiation

Sammanfattning: Certain diseases in the larynx like epiglottitis, false croup, and allergic reactions lead to local edema, which may result in respiratory distress. The pathophysiology of the various types of edema in the larynx is mainly unknown. Mast cells may be one factor, as they occur throughout the airways and are involved in allergic reactions with release of several mediators inducing smooth muscle contraction, vasodilatation, mucus secretion and edema. The airways are also richly innervated with nerve fibers containing several different neuropeptides, of which some degranulate mast cells and have trophic actions. In general, irradiation is an important part in treatment of laryngeal carcinoma. The irradiation regime affects the entire larynx and is often leading to serious discomfort for the patient. In an experimental model system on the rat larynx, and by use of compound 48/80, dexamethasone, capsaicin and the neuropeptide SP, one aim of the present study was to characterize the laryngeal mast cells and to ascertain their role in the formation of laryngeal edema. Furthermore, to examine the morphological changes that occur in the normal laryngeal tissue after irradiation with special reference to mast cells and changes tn the pattern of neuropeptide immunoreactivity. The techniques used were immunohistochemistry, radioimmunoassay (RlA), light- and electron microscopy. There was a large regional variation in the distribution of mucosal mast cells (MMCs) and connective tissue mast cells (CTMCs) in the rat larynx. In the epiglottis, MMCs was preferentially found in the epithelium, and CTMCs tn the lamina propria of the laryngeal side. In the subglottic region, there were numerous MMCs in the epithelium and very few CTMCs in the lamina propria. Intravenous injection of the mast cell activator compound 48/80 induced CTMC degranulation and increased vascular permeability in venules as seen by Monastral blue. This induced edema on the lingual side of the epiglottis and edema in the lateral parts of the subglottic region with a concomitant subepithelial exudate. After SP and capsaicin injections, there was an increased permeability in venules: a subglottic exudate subepithelially but no edema in the epiglottis. The reason for the swelling preferentially on the lingual side of the epiglottis was presumably an increased vascular permeability in combination with a loose connective tissue and an impermeable epithelium. Ten days after irradiation of the larynx, there was an increase in substance P-, bombesin- and enkephalin like-immunoreactivity in local ganglionic cells and in nerve fibers surrounding the subglottic acini. The increase in levels of bombesin-like peptide was verifled by RIA. Simultaneously there were ultrastructural changes tn the granules of the serous and mucous actni. The MMCs and CTMCs were reduced in number. Four-six months after irradiation, there was an increase in connective tissue and a reduced number of subglottic acini. Ultrastructural changes were still visible in the granules, while the number of mast cells and the pattern of expression of the neuropeptides was the same as in controls. It seems that the irradiation effect on mast cells and neuropeptides is time related and that there is a relationship between the affection of the glandular structure and the change in neuropeptide expression. ISBN 91-628-2911-4