Animal Models of Chronic Airways Injury

¹ The Boston VA Medical Center, the Pulmonary Center and the Departments of Medicine and Biochemistry, Boston University School of Medicine and the Tufts University School of Medicine, Boston.

Airways SCM is induced by a wide variety of noxious agents that perturb but do not kill the epithelial cells. Discharge of mucus soon after first exposure to a noxious agent is frequently observed, but discharge of mucus may or may not be followed by development of SCM. Treatment with steroidal and nonsteroidal antiinflammatory agents protects against development of SCM in some models, such as tobacco smoke-induced SCM, but not in others, such as enzyme-induced SCM. In general, SCM regresses slowly or not at all spontaneously. Recovery of some models, such as tobacco smoke-induced SCM, is hastened by nonsteroidal antiinflammatory agents. Experimental protection against induction of enzyme-induced SCM by secretory leukocyte protease inhibitor, which is secreted by airways secretory cells, suggests that such protection may be the in vivo role of that antiprotease. The response of the airways to injury is heterogeneous, with patterns of response of the secretory cells varying according to agent, species, and longitudinal localization of epithelial cells in the airways. The longitudinal heterogeneity of response of secretory epithelial cells to injury is summarized in Table 1. Anatomic heterogeneity of epithelial cells may make a minor contribution to longitudinal variation in response of secretory cells to injury. Molecular heterogeneity of the cellular milieu seems the more likely explanation for this variation in cellular response.