Factors modulating the epithelial response to toxicants in tracheobronchial airways
Introduction
The respiratory system is exposed to a wide variety of environmental contaminants. The cellular and architectural complexity of this system establishes a wide range of microenvironments with different cellular composition and response to environmental stressors. The variable nature of the response is consistent regardless of whether the route of exposure is via inhaled air or the vascular system. More than 40 cell phenotypes found in the lungs are not uniform either in their distribution throughout the organ or in their response to toxicants. This is especially true for target cell populations that occupy the tracheobronchial airway tree. Increasing evidence strongly suggests that cell populations within the tracheobronchial airways establish distinct microenvironments that vary markedly in their steady state biological activity and in their potential for response to environmental stressors. The composition of the entire airway wall appears to contribute to the steady state function of all of the cell populations within the local environment. In addition, all the cell populations appear to respond to stress even when only one subpopulation is targeted. This discussion will first address the concept of the organization of an airway wall as a microenvironment of complex cellular and acellular composition with strong trophic interactions. In addition, the current state of our understanding of the biological factors, which modulate the response of these individual microenvironments as targets of toxic injury, will be defined.
Section snippets
Epithelial–mesenchymal trophic unit as a paradigm
The concept of the epithelial–mesenchymal trophic unit was developed as a framework for defining the cellular and metabolic mechanisms regulating the response to toxic injury in a complex biological structure such as the tracheobronchial airway tree (Evans et al., 1999, Holgate, 2000). Each segment, or airway generation, within the branching pattern is addressed as a unique biological entity whose properties may differ from those of neighboring branches. The portions of the airways between
Modulating factors
Using the concept that the cellular population which organizes a conducting airway as a biological entity unique to a particular branch of the airway tree emphasizes the number of factors by which they differ in their pathobiological response to toxic injury, including susceptibility to acute injury, the pattern of repair and the development of tolerance. Issues to be considered include: airway microenvironment, the status of differentiation based on animal age, the history of previous exposure
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