Allergic inflammation induces a persistent mechanistic switch in thromboxane-mediated airway constriction in the mouse.

Journal Article (Journal Article)

Actions of thromboxane (TXA(2)) to alter airway resistance were first identified over 25 years ago. However, the mechanism underlying this physiological response has remained largely undefined. Here we address this question using a novel panel of mice in which expression of the thromboxane receptor (TP) has been genetically manipulated. We show that the response of the airways to TXA(2) is complex: it depends on expression of other G protein-coupled receptors but also on the physiological context of the signal. In the healthy airway, TXA(2)-mediated airway constriction depends on expression of TP receptors by smooth muscle cells. In contrast, in the inflamed lung, the direct actions of TXA(2) on smooth muscle cell TP receptors no longer contribute to bronchoconstriction. Instead, in allergic lung disease, TXA(2)-mediated airway constriction depends on neuronal TP receptors. Furthermore, this mechanistic switch persists long after resolution of pulmonary inflammation. Our findings demonstrate the powerful ability of lung inflammation to modify pathways leading to airway constriction, resulting in persistent changes in mechanisms of airway reactivity to key bronchoconstrictors. Such alterations are likely to shape the pathogenesis of asthmatic lung disease.

Full Text

Duke Authors

Cited Authors

  • Cyphert, JM; Allen, IC; Church, RJ; Latour, AM; Snouwaert, JN; Coffman, TM; Koller, BH

Published Date

  • January 1, 2012

Published In

Volume / Issue

  • 302 / 1

Start / End Page

  • L140 - L151

PubMed ID

  • 21984570

Pubmed Central ID

  • PMC3349367

Electronic International Standard Serial Number (EISSN)

  • 1522-1504

Digital Object Identifier (DOI)

  • 10.1152/ajplung.00152.2011


  • eng

Conference Location

  • United States