Continuous XXXX synthesis by inducible @entity842 synthase in normal @entity1 airway epithelium in vivo.

@entity1 @entity32 @entity842 @entity1030 @entity3623
@entity842 (NO) is an important mediator of inflammatory responses in the lung and a key regulator of bronchomotor tone. An airway @entity3623 ( @entity3623 ; EC 1.14.13.39) has been proposed as a source of endogenous NO in the lung but has not been clearly defined. Through molecular cloning, we conclusively demonstrate that NO synthesis in normal @entity1 airways is due to the continuous expression of the @entity3623 ( @entity3623 ) isoform in airway epithelial cells. Although @entity3623 mRNA expression is abundant in airway epithelial cells, expression is not detected in other pulmonary cell types, indicating that airway epithelial cells are unique in the continuous pattern of @entity3623 expression in the lung. In situ analysis reveals all airway epithelial cell types express @entity3623 . However, removal of epithelial cells from the in vivo airway environment leads to rapid loss of @entity3623 expression, which suggests expression is dependent upon conditions and/or factors present in the airway. Quantitation of @entity3623 activity in epithelial cell lysates indicates nanomolar levels of NO synthesis occur in vivo. Remarkably, the high-level @entity3623 expression is constant in airway epithelium of normal individuals over time. However, expression is strikingly decreased by inhaled corticosteroids and beta-adrenergic agonists, medications commonly used in treatment of inflammatory @entity1030 . Based upon these findings, we propose that respiratory epithelial cells are key inflammatory cells in the airway, functioning in host defense and potentially playing a role in airway @entity32 .
