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Am J Physiol Lung Cell Mol Physiol (January 4, 2002). doi:10.1152/ajplung.00323.2001
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Articles in PresS, published online ahead of print January 4, 2002
Am J Physiol Lung Cell Mol Physiol, 10.1152/ajplung.00323.2001
Submitted on August 13, 2001
Accepted on December 14, 2001

Leukotrienes mediate neurogenic inflammation in lungs of young rats infected with respiratory syncytial virus

Katrin Wedde-Beer1, Chengping Hu1, Maria M Rodriguez2, and Giovanni Piedimonte3*

1 Pediatrics, University of Miami, Miami, Florida, USA
2 Pathology, University of Miami, Miami, Florida, USA; Pediatrics, University of Miami, Miami, Florida, USA
3 Pediatrics, University of Miami, Miami, Florida, USA; Medicine, University of Miami, Miami, Florida, USA; Molecular/Cellular Pharmacology, University of Miami, Miami, Florida, USA

* To whom correspondence should be addressed. E-mail: gpiedimo{at}med.miami.edu.

Respiratory syncytial virus (RSV) infection potentiates neurogenic inflammation in rat airways. Because some vascular effects of sensory nerves are mediated by cysteinyl leukotrienes (cysLTs), we studied whether the receptor antagonist montelukast inhibits neurogenic plasma extravasation in RSV-infected rats. Pathogen-free rats were inoculated at 2 wk (weanlings) or 12 wk (adults) of age with RSV or virus-free medium and treated with montelukast or its vehicle starting 1 day before inoculation. Five days post-inoculation, we measured the extravasation of Evans blue-labeled albumin in the respiratory tract after stimulation of sensory nerves with capsaicin. Montelukast had no effect in the extrapulmonary airways, but abolished albumin extravasation in the intrapulmonary airways of RSV-infected rats, with a larger effect in weanlings than in adults. Increased concentrations of 5-lipoxygenase (5-LO)-encoding mRNA and cysLTs, as well as numerous mast cell were detected in the lung tissues of RSV-infected weanling rats. These observations suggest that the release of neuropeptides from capsaicin-sensitive sensory nerves and non-neuronal cells in the lungs of RSV-infected young rats increases vascular permeability by promoting the release of leukotrienes from mast cells.




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