The airway epithelium: Structural and functional properties in health and disease

Abstract

The airway epithelium: Structural and functional properties in health and diseaseKNIGHT DA, HOLGATE ST. Respirology 2003; 8: 432-446 Abstract: The major function of the respiratory epithelium was once thought to be that of a physical barrier. However, it constitutes the interface between the internal milieu and the external environment as well as being a primary target for inhaled respiratory drugs. It also responds to changes in the external environment by secreting a large number of molecules and mediators that signal to cells of the immune system and underlying mesenchyme. Thus, the epithelium is in a unique position to translate gene-environment interactions. Normally, the epithelium has a tremendous capacity to repair itself following injury. However, evidence is rapidly accumulating to show that the airway epithelium of asthmatics is abnormal and has increased susceptibility to injury compared to normal epithelium. Areas of detachment and fragility are a characteristic feature not observed in other inflammatory diseases such as COPD. In addition to being more susceptible to damage, normal repair processes are also compromised. Failure of appropriate growth and differentiation of airway epithelial cells will cause persistent mucosal injury. The response to traditional therapy such as glucocorticoids may also be compromised. However, whether the differences observed in asthmatic epithelium are a cause of or secondary to the development of the disease remains unanswered. Strategies to address this question include careful examination of the ontogeny of the disease in children and use of gene array technology should provide some important answers, as well as allow a better understanding of the critical role that the epithelium plays under normal conditions and in diseases such as asthma.

NADPH oxidases in lung biology and pathology: Host defense enzymes, and more

“…Moreover, the airway epithelium also generates airway mucins that facilitate mucociliary clearance of inhaled particulates or microorganisms (103,104). Recent studies suggest that DUOX may participate in these responses as well, as illustrated by DUOX1-mediated production of epithelial mucins, such as MUC1 and MUC5AC, in response to inflammatory mediators such as neutrophil elastase or tumor necrosis factor (TNF)-α (105,106).…”

“…1), which are critically involved in cell growth and differentiation and morphogenesis (13,38,52,110,111). Because the airway epithelium is continuously subjected to injury due to environmental stress, it possesses an exceptional capacity to repair itself (112,113), through a coordinated response involving rapid spreading and migration of neighboring cells, cell proliferation and redifferentiation, to restore the original mucociliary epithelium (103,114,115). Using in vitro wound models in cultured airway epithelial systems, DUOX1 was found to play a critical role in cell migration as part of the wound repair response (87,108), illustrating an additional function of DUOX1 in maintenance of epithelial integrity.…”

Cigarette smoking induces small airway epithelial epigenetic changes with corresponding modulation of gene expression

“…In humans, the SAE consists of four major cell types: ciliated, secretory, columnar and basal cells (30,33). These cells provide a barrier and innate immunity that protect the airway from environmental stressors, pollutants and pathogens (34)(35)(36). Cigarette smoking is associated with disordering of the differentiation of the SAE basal cells, with consequent disordered function of the airway mucociliary barrier (34,35).…”

“…Cigarette smoking is associated with disordering of the differentiation of the SAE basal cells, with consequent disordered function of the airway mucociliary barrier (34,35). The ability of the SAE to alter gene expression in response to external stimuli is critical to airway defense and repair mechanisms (30,31,34,36).…”

Flow Cytometric Isolation of Primary Murine Type II Alveolar Epithelial Cells for Functional and Molecular Studies

“…AECII have been shown to participate in cytokine production in inflamed airways and to even act as antigenpresenting cells in both infection and T-cell mediated autoimmunity [1][2][3][4][5][6][7][8] . Therefore, they are especially interesting also in clinical contexts such as airway hyper-reactivity to foreign and self-antigens as well as infections that directly or indirectly target AECII.…”