Mucous membrane of respiratory epithelium.

Abstract

Of the eight epithelial cell types of the airway surface epithelium three are secretory, the mucous, serous and Clara cells: the first two are also found in the submucosal glands. Organ culture results indicate that the pattern ofcontrol of the surface cells is different from that of the glands. Our recent studies show that in the surface epithelium Clara and serous cells can quickly convert to mucous as do nonsecretory undifferentiated cells. The balance between the various cell types changes with airway level. The type of glycoprotein within the secretory granules is neutral or acid, sialylated or sulfated, and also shows a regional pattern. Homeostasis is maintained in the normal but the equilibrium is quickly upset by a variety of irritants, infection or drugs. Change in pattern of glycoprotein synthesis depends largely on change of granules. The granules at the cell apex change first. The nature and distribution of the various receptor binding sites is significant in patterns of control. This lability occurs in an intact epithelium and whether or not mitotic activity is increased. With irritation tolerance to stimulus develops. Anti-inflammatory agents can protect against some of these cellular and intracellular events. Our organ culture studies and biochemical analysis of secretion complement the tissue studies. Recent studies show that isoproterenol and salbutamol (a nonselective ,B agonist and a selective (2, respectively) alter the normal mix ofcell types and quickly, but that they have different regional specificity. Although there are animal models in which the airway damage is associated with necrosis and sloughing of epithelium, this report concentrates on animal models in which the nature and dose of the damaging agent are such that the epithelium remains intact. Such models are especially relevant to understanding the effect of a relatively low dose of irritants whether delivered in acute or chronic exposure. It is a remodelling of the cell population of the normal intact epithelium that occurs, one that is particularly related to mucus hypersecretion, doubtless the most obvious single feature of the response and almost certainly the most important functionally (1, 2). Even when the injury is serious enough to cause ulceration we have shown healing occurs while the administration of the irritant continues and in the new epithelium a similar remodelling is seen to that discussed below (3). Our most recent studies show that changes that we identify with chronic irritation occur quickly, much more quickly than previously suspected (4, 5). In such studies it is essential to use animals with