Sensory nerves promote ozone-induced lung inflammation in mice.
Genetically manipulated mice exhibiting altered innervation of the airways were used to examine the role of sensory nerves in ozone-induced lung inflammation. Transgenic mice expressing nerve growth factor (NGF) from the lung-specific Clara cell secretory protein (CCSP) promoter exhibit hyperinnervation of the airways by sympathetic and tachykinin-containing sensory nerve fibers. Mice carrying a mutation in the low-affinity NGF receptor (NGFR) gene possess deficits in sensory innervation. CCSP-NGF transgenic mice exhibited a twofold increase in the number of lung lavage neutrophil level whereas NGFR knockout mice exhibited a nearly 50% decrease in neutrophilic inflammation compared with wild-type mice 18 h after ozone inhalation. Treatment with neurokinin receptor antagonists reduced the level of neutrophilic inflammation in both wild-type and CCSP-NGF mice. Examination of lavage fluid cytokine concentrations revealed that 4 h after ozone exposure CCSP-NGF mice produced significantly higher amounts of the chemokine KC than wild-type mice exposed to ozone. The results of this study indicate that sensory nerves are important mediators of ozone-induced inflammation in mice.
Graham
R M
RM
Section of Pulmonary Diseases, Critical Care and Environmental Medicine, Tulane University Health Sciences Center, 1430 Tulane Avenue, New Orleans, LA 70112, USA.
Friedman
M
M
Hoyle
G W
GW
D000818:Animals; D051379:Mice; D008822:Mice, Transgenic; D010126:Ozone / Q000494:pharmacology*; D011014:Pneumonia / Q000139:chemically induced*; D012137:Respiratory System / Q000187:drug effects* / Q000294:innervation*
D010126:Ozone