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Trypsin and mast cell tryptase can signal to epithelial cells, myocytes, and nerve fibers of the respiratory tract by cleaving proteinase-activated receptor 2 (PAR2). Since tryptase inhibitors are under development to treat asthma, a precise understanding of the contribution of PAR2 to airway inflammation is required. We examined the role of PAR2 in allergic inflammation of the airway by comparing OVA-sensitized and -challenged mice lacking or overexpressing PAR2. In wild-type mice, immunoreactive PAR2 was detected in airway epithelial cells and myocytes, and intranasal administration of a PAR2 agonist stimulated macrophage infiltration into bronchoalveolar lavage fluid. OVA challenge of immunized wild-type mice stimulated infiltration of leukocytes into bronchoalveolar lavage and induced airway hyperreactivity to inhaled methacholine. Compared with wild-type animals, eosinophil infiltration was inhibited by 73% in mice lacking PAR2 and increased by 88% in mice overexpressing PAR2. Similarly, compared with wild-type animals, airway hyperreactivity to inhaled methacholine (40 μg/ml) was diminished 38% in mice lacking PAR2 and increased by 52% in mice overexpressing PAR2. PAR2 deletion also reduced IgE levels to OVA sensitization by 4-fold compared with those of wild-type animals. Thus, PAR2 contributes to the development of immunity and to allergic inflammation of the airway. Our results support the proposal that tryptase inhibitors and PAR2 antagonists may be useful therapies for inflammatory airway disease.

This article examines agency mortality between 1946 and 1997 and argues that, contrary to popular belief, agencies are not immortal. Rather, agencies face significant risks of termination, particularly due to political turnover. When an agency's opponents gain power, the hazards of agency mortality increase. Principal among the findings of this paper are that 62% of agencies created since 1946 have been terminated and that political turnover is one of the primary causes of termination.

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The study of bureaucracies and their relationship to political actors is central to understanding the policy process in the United States. Studying this aspect of American politics is difficult because theories of agency behavior, effectiveness, and control often require measures of administrative agencies' policy preferences, and appropriate measures are hard to find for a broad spectrum of agencies. We propose a method for measuring agency preferences based upon an expert survey of agency preferences for 82 executive agencies in existence between 1988 and 2005. We use a multirater item response model to provide a principled structure for combining subjective ratings based on scholarly and journalistic expertise with objective data on agency characteristics. We compare the resulting agency preference estimates and standard errors to existing alternative measures, discussing both the advantages and limitations of the method.