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Am J Physiol Lung Cell Mol Physiol (March 8, 2002). doi:10.1152/ajplung.00414.2001
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Articles in PresS, published online ahead of print March 8, 2002
Am J Physiol Lung Cell Mol Physiol, 10.1152/ajplung.00414.2001
Submitted on October 24, 2001
Accepted on March 2, 2002

Nerve Growth Factor (NGF) and NGF Receptors in Respiratory Syncytial Virus (RSV)-Infected Lungs

Chengping Hu1, Katrin Wedde-Beer1, Alexander Auais1, Maria M Rodriguez2, and Giovanni Piedimonte3*

1 Pediatrics, University of Miami, Miami, Florida, USA
2 Pediatrics, University of Miami, Miami, Florida, USA; Pathology, 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.

Nerve growth factor (NGF) controls sensorineural development and responsiveness and modulates immuno-inflammatory reactions. Respiratory syncytial virus (RSV) potentiates the proinflammatory effects of sensory nerves in rat airways by upregulating the substance P (NK1) receptor. We investigated whether the expression of NGF and its trkA and p75 receptors in the lungs is age-dependent, whether it is upregulated during RSV infection, and whether it affects neurogenic inflammation. Pathogen-free rats were killed at 2 (weanling) to 12 (adult) wk of age; in addition, subgroups of rats were inoculated with RSV or virus-free medium. In pathogen-free rats, expression of NGF and its receptors in the lungs declined with age, but RSV doubled expression of NGF, trkA, and p75 in weanling and adult rats. Exogenous NGF upregulated NK1 receptor expression in the lungs. Anti-NGF antibody inhibited NK1 receptor upregulation and neurogenic inflammation in RSV-infected lungs. These data indicate that expression of NGF and its receptors in the lungs declines physiologically with age, but is upregulated by RSV and is a major determinant of neurogenic inflammation.




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