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Am J Physiol Lung Cell Mol Physiol (April 5, 2002). doi:10.1152/ajplung.00446.2001
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Articles in PresS, published online ahead of print April 5, 2002
Am J Physiol Lung Cell Mol Physiol, 10.1152/ajplung.00446.2001
Submitted on December 3, 2001
Accepted on April 3, 2002

Heme oxygenase modulates oxidant-signaled airway smooth muscle contractility : role of bilirubin

Abdoulaye Samb1, Camille Taille1*, Abdelhamid Almolki1, Jerome Megret1, James M. Staddon2, Michel Aubier1, and Jorge Boczkowski1

1 INSERM, INSERM U 408, Paris, France, Metropolitan
2 Eisai London Research Laboratories Ltd., University College London, London, United Kingdom

* To whom correspondence should be addressed. E-mail: c-taille{at}bichat.inserm.fr.

Reactive oxygen species (ROS) increase the contractile response of airway smooth muscle (ASM). Heme-oxygenase (HO) catabolises heme to the powerful antioxidant bilirubin. As HO is expressed in the airways, we investigated its effects on ASM contractility and ROS production in guinea pig trachea. HO expression was higher in the epithelium than in tracheal smooth muscle (TSM). Incubation of tracheal rings (TR) with the HO inhibitor SnPP IX or the HO substrate hemin increased and decreased respectively ASM contractile response to carbamylcholine. The effect of hemin was reversed by SnPP and mimicked by the antioxidants Superoxide Dismutase (SOD) and Catalase. Hemin significantly reduced the effect of carbamylcholine in rings treated with the guanylate cyclase inhibitor ODQ , as compared to ODQ-treated rings without hemin incubation, suggesting that the CO-cGMP pathway was not involved in the control of tracheal reactivity. SnPP and hemin increased and decreased ROS production by TR by 18% and 38% respectively. Bilirubin (100 pM) significantly decreased TR contractility and ROS production. Hemin, bilirubin and SOD/Catalase decreased phosphorylation of the contractile protein myosin light chain, whereas SnPP significantly augmented it. These data suggest that modulation of the redox status by HO, and moreover by bilirubin, modulates airway smooth muscle contractility by modulating levels of phosphorylated myosin light chain.




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