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Am J Physiol Lung Cell Mol Physiol (March 14, 2003). doi:10.1152/ajplung.00004.2003
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Submitted on January 8, 2003
Accepted on March 6, 2003

IMMUNOMODULATORY EFFECTS OF SENSORY NERVES DURING RESPIRATORY SYNCYTIAL VIRUS INFECTION IN RATS

Alexander Auais1, Becky Adkins2, Galia Napchan1, and Giovanni Piedimonte3*

1 Department of Pediatrics, University of Miami, Miami, Florida, USA
2 Department of Microbiology/Immunology, University of Miami, Miami, Florida, USA
3 Department of Pediatrics, University of Miami, Miami, Florida, USA; Department of Medicine, University of Miami, Miami, Florida, USA; Department of 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 is associated with exaggerated neurogenic inflammation in the airways. This study sought to determine whether irritation of the mucosal sensory fibers affects the recruitment of lymphocytes and monocytes to RSV-infected airways. Pathogen-free rats were inoculated with RSV or with virus-free medium and were injected 5 days later with capsaicin to stimulate airway sensory nerves. Broncho-alveolar lavage was performed 1, 5, or 10 days after nerve stimulation and samples were analyzed by differential cell count and flow cytometry. Without nerve stimulation, RSV caused minimal increase in the number of lymphocytes and monocytes above pathogen-free control levels. After nerve stimulation, numerous lymphocytes, predominantly CD4+ T cells, and monocytes were recruited into the airways of infected rats, whereas no difference was found in pathogen-free controls. RSV induced overexpression of the NK1 receptor for substance P on discrete lymphocyte subpopulations within the bronchial-associated lymphoid tissue (BALT) and treatment with a specific NK1 receptor antagonist abolished the recruitment of both lymphocytes and monocytes to infected airways. Our data suggest that airborne irritants stimulating mucosal sensory fibers during RSV infection exert important immunomodulatory effects by attracting to the infected airways selected lymphocyte subpopulations from the local BALT as well as monocytes.




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