Nerve growth factor and nerve growth factor receptors in respiratory syncytial virus-infected lungs.
Nerve growth factor (NGF) controls sensorineural development and responsiveness and modulates immunoinflammatory reactions. Respiratory syncytial virus (RSV) potentiates the proinflammatory effects of sensory nerves in rat airways by upregulating the substance P receptor, neurokinin 1 (NK(1)). 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 NK(1) receptor expression in the lungs. Anti-NGF antibody inhibited NK(1) 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.
Department of Pediatrics, University of Miami School of Medicine, Miami, Florida 33136, USA.
Chengping
C
Hu
Katrin
K
Wedde-Beer
Alexander
A
Auais
Maria M
MM
Rodriguez
Giovanni
G
Piedimonte
D000375:Aging / Q000378:metabolism; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D005260:Female; D008168:Lung / Q000378:metabolism*; D008297:Male; D020932:Nerve Growth Factor / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D020078:Neurogenic Inflammation / Q000503:physiopathology / Q000821:virology; D011014:Pneumonia / Q000503:physiopathology / Q000821:virology; D051381:Rats; D011916:Rats, Inbred F344; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism*; D018040:Receptors, Neurokinin-1 / Q000378:metabolism; D012016:Reference Values; D018357:Respiratory Syncytial Virus Infections / Q000378:metabolism*
D000906:Antibodies; D017475:Receptors, Nerve Growth Factor; D018040:Receptors, Neurokinin-1; D020932:Nerve Growth Factor