Neurotransmitters in airway parasympathetic neurons altered by neurotrophin-3 and repeated allergen challenge.
Changes in airway nerves associated with chronic inflammation may underlie the pathogenesis and symptoms of lower airway diseases, such as asthma. The molecules most likely causing such alterations are neurotrophins (NTs) and/or related neurokines. In several species, including humans, lower airway parasympathetic postganglionic neurons that project axons to airway smooth muscle are either cholinergic or nonadrenergic noncholinergic (NANC), the latter synthesizing vasoactive intestinal peptide and nitric oxide, but not acetylcholine. In guinea pig trachealis smooth muscle, cholinergic nerve terminals arise from ganglionic neurons located near the tracheal smooth muscle, whereas the source of NANC nerve fibers is from neurons in ganglia located in the adjacent myenteric plexus of the esophagus, making this an ideal species to study regulation of parasympathetic neurotransmitter phenotypes. In the present study, we determined that, 48 hours after repeated allergen challenge, the NANC phenotype of airway parasympathetic ganglionic neurons changed to a cholinergic phenotype, and NT-3 mimicked this change. Nerve growth factor, brain-derived neurotrophic factor, leukemia inhibitory factor, or IL-1β had no effect on either phenotype, and they did not induce these neurons to synthesize substance P or tyrosine hydroxylase. These results indicate a role for inflammation and NT-3 in regulating biochemical and anatomical characteristics of principal neurons in adult airway parasympathetic ganglia.
Pan
Jenny
J
Division of Allergy and Clinical Immunology, the Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA.
Rhode
Holly K
HK
Undem
Bradley J
BJ
Myers
Allen C
AC
D000485:Allergens / Q000276:immunology*; D000818:Animals; D004947:Esophagus / Q000294:innervation / Q000473:pathology; D005455:Fluorescent Antibody Technique; D005629:Frozen Sections; D006168:Guinea Pigs; D008168:Lung / Q000276:immunology* / Q000294:innervation*; D008297:Male; D009474:Neurons / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D018377:Neurotransmitter Agents / Q000378:metabolism*; D020933:Neurotrophin 3 / Q000378:metabolism*; D010275:Parasympathetic Nervous System / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D011014:Pneumonia / Q000276:immunology / Q000473:pathology
D000485:Allergens; D018377:Neurotransmitter Agents; D020933:Neurotrophin 3