Mechanisms of asthma and allergic inflammationProasthmatic effects and mechanisms of action of the dust mite allergen, Der p 1, in airway smooth muscle
Section snippets
Animals
Thirty-four adult New Zealand White rabbits were used in this study, which was approved by the Biosafety and Animal Research Committee of the Joseph Stokes Research Institute at Children's Hospital of Philadelphia. The animals had no signs of respiratory disease for several weeks before the study, and their care and use were in accordance with the Guide for the Care and Use of Laboratory Animals prepared by the Institute of Laboratory Animal Resources, National Research Council.
Preparation and Der p 1 treatment of rabbit ASM tissues
After general
Effects of Der p 1 on rabbit ASM responsiveness
To assess the effects of Der p 1 on ASM responsiveness, agonist-mediated constrictor and relaxation responses were compared in control and Der p 1–exposed isolated rabbit ASM segments, both in the absence and presence of E-64 (1 μmol/L). As shown in Fig 1, relative to control tissues, ASM segments exposed to a maximally effective dose of Der p 1 (ie, 1 μg/mL) exhibited increased constrictor responses to exogenously administered acetylcholine. Accordingly, relative to the mean ± SE maximal
Discussion
To our knowledge, the results of the current study are the first to demonstrate that the ubiquitous aeroallergen, Der p 1, can directly exert proasthmatic-like effects on ASM function that are characterized by enhanced agonist-mediated ASM contractility and impaired β-adrenoceptor–mediated ASM relaxation. Our observed actions of purified Der p 1 on ASM function were attributed to its intrinsic cysteine protease activity, because the induced changes in ASM responsiveness were largely prevented
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Supported by National Heart, Lung, and Blood Institute grants HL-31467 and HL-61038.