Epithelial injury

Bronchial Asthma. Figure 2 Mechanisms of bronchial hyperresponsiveness. Toxic products from eosinophils [cationic peptides, reactive oxygen species (ROS)] cause epithelial injury. Nerve endings become easily accessible to mediators from mast cells, eosinophils [eosinophil-derived neurotoxin (EDN)], and neutrophils, and to airborne toxicants such as S02. Activation of nerve endings stimulates effector cells like mucosal glands and airway smooth muscle either directly or by cholinergic reflexes. 

Fibrotic disease results from epithelial injury and abnormal wound repair in the absence of preceding inflammation. 

ChangLai SP, Hung WT, Liao KK (1999) Detecting alveolar epithelial injury following volatile anesthetics by "mTc DTPA radioaerosol inhalation lung scan. Respiration 66 506-510. 

Prolonged skin contact may cause dermatitis. The liquid in the eye causes an immediate burning sensation, followed by corneal epithelial injury and conjunctival edema. ... 

The ulcer may be sterile. Stromal breakdown and progressive ulceration is largely driven by matrix metalloproteinases (MMPs) and serine proteases derived from local comeal cells and from leukocytes sequestered in the cornea in response to the initial injury (Fig. 13.1). Inoculation and replication of pathogenic bacteria at the site of minor epithelial injury releases exotoxins and microbial proteases that potentiate the initial processes of comeal breakdown and amplify endogenous stromal hydrolysis. However, once started, an ulcer can evolve its own biochemical momentum based... 

Eosinophil Major Basic Protein 195 7. Repair of Epithelial Injury 199... 

However, the importance of the airway epithelium in the homeostatic control of underlying tissues may be at a rather more fundamental level than the acute changes in sensitivity of airways smooth muscle produced by acute epithelial injury or removal. The airway epithelium is now recognized to be an important source of growth factors [including interleukins (IL)-1, -4, -6,... 

Only few detailed analyses of the intracellular events following epithelial injury have been performed using cells from the airways, and most mechanistic work has concentrated on pre-necrotic and necrotic processes in epitheUal cells of renal origin (Trump etal., 1980, 1981 Trump and Berezesky, 1984). Collectively these studies, which have employed a wide range of stimuli to evoke cellular injury (ischaemia, metabolic poisons, chaotropic agents and ionophores), suggest that similar patterns of intracellular events accompany injury evoked by the different stimuli. 

An early intracellular response to epithelial injury appears to involve an increase in intracellular Ca which coincides with the failure of the cells to regulate Na" ... 

Much of the intracellular response to epithelial injury remains to be defined. The mechanistic hnkages between those ionic and morphological changes that have been... 

Cell-derived Mediators Implicated in Epithelial Injury... 

There is no doubt that eosinophils are capable of causing epithelial injury (see e.g. Plate III and Fig. 10.5). The precise combination of mediators that contribute to this process are not known, but much attention has been paid to protein components of eosinophil granules. 

Grimaud, 1990) that they should be of fundamental importance in diseases associated with remodelling and fibrosis of the basement membrane, epithelial injury and fibrosis. 

From the pharmacological standpoint, the process of epithelial injury perse has received Utde direct attention. This situation is not difficult to understand, because our level of ignorance about many of the basic cell and molecular processes impedes a rational attempt at designing strategies for the manipulation of chronic injury and... 

Research on epithelial injury in the author s laboratory was supported by the Medical Research Council, The National Asthma Campaign, The British Lung Foundation and The Royal Society. Special thanks are due to Carolyn Herbert, Patrick Ring and Julia Carver who have been centrally involved in undertaking studies on mucosal injury in the author s laboratory. I would like to thank Kemi Olaniyan for her assistance in preparation of the manuscript. 

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