Role of intrinsic airway neurons in ozone-induced airway hyperresponsiveness in ferret trachea

Wu, Zhong-Xin; Maize, David F.; Satterfield, Brian E.; Frazer, David G.; Fedan, J S; Dey, Richard D.

doi:10.1152/jappl.2001.91.1.371

Cited by 23 publications

(36 citation statements)

References 39 publications

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“…Therefore, our initial studies examined the normal developmental changes that occur in SP airway innervation throughout the first month of postnatal life. Changes in SP-containing nerves were measured because of their well established role in regulating airway responses to irritants such as O 3 (38,39). The results show that SP-containing nerve fibers in the extrapulmonary epithelium and lamina propria increased threefold from PD1 through PD15, and were maintained through PD29 (Figure 2A).…”

Section: Discussionmentioning

confidence: 98%

Sensory Neural Responses to Ozone Exposure during Early Postnatal Development in Rat Airways

Hunter

Dey

2010

Am J Respir Cell Mol Biol

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Airway infections or irritant exposures during early postnatal periods may contribute to the onset of childhood asthma. The purpose of this study was to examine critical periods of postnatal airway development during which ozone (O 3 ) exposure leads to heightened neural responses. Rats were exposed to O 3 (2 ppm) or filtered air for 1 hour on specific postnatal days (PDs) between PD1 and PD29, and killed 24 hours after exposure. In a second experiment, rats were exposed to O 3 on PD2-PD6, inside a proposed critical period of development, or on PD19-PD23, outside the critical period. Both groups were reexposed to O 3 on PD28, and killed 24 hours later. Airways were removed, fixed, and prepared for substance P (SP) immunocytochemistry. SP nerve fiber density (NFD) in control extrapulmonary (EXP) epithelium/lamina propria (EPLP) increased threefold, from 1% to 3.3% from PD1-PD3 through PD13-PD15, and maintained through PD29. Upon O 3 exposure, SP-NFD in EXP-smooth muscle (SM) and intrapulmonary (INT)-SM increased at least twofold at PD1-PD3 through PD13-PD15 in comparison to air exposure. No change was observed at PD21-PD22 or PD28-PD29. In critical period studies, SP-NFD in the INT-SM and EXP-SM of the PD2-PD6 O 3 group re-exposed to O 3 on PD28 was significantly higher than that of the group exposed at PD19-PD23 and re-exposed at PD28. These findings suggest that O 3 -mediated changes in sensory innervation of SM are more responsive during earlier postnatal development. Enhanced responsiveness of airway sensory nerves may be a contributing mechanism of increased susceptibility to environmental exposures observed in human infants and children.

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Section: Discussionmentioning

confidence: 98%

Sensory Neural Responses to Ozone Exposure during Early Postnatal Development in Rat Airways

Hunter

Dey

2010

Am J Respir Cell Mol Biol

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“…In some experiments, CP-99994 (3 ϫ 10 Ϫ6 M) was added to the culture media 30 min before IL-1␤ and maintained throughout the experiment to determine the role of SP in intrinsic airway neurons. The antagonist concentration was based on previous studies (28,51,55). The petri dishes were then placed in a controlled atmosphere culture chamber and gassed with a mixture of 95% O2 and 5% CO2.…”

Section: Methodsmentioning

confidence: 99%

Interleukin-1β-induced airway hyperresponsiveness enhances substance P in intrinsic neurons of ferret airway

Satterfield

Fedan

et al. 2002

American Journal of Physiology-Lung Cellular and Molecular Phys

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Dey. Interleukin-1␤-induced airway hyperresponsiveness enhances substance P in intrinsic neurons of ferret airway. Am J Physiol Lung Cell Mol Physiol 283: L909-L917, 2002. First published April 12, 2002 10.1152/ajplung.00363.2001.-Interleukin (IL)-1␤ causes airway inflammation, enhances airway smooth muscle responsiveness, and alters neurotransmitter expression in sensory, sympathetic, and myenteric neurons. This study examines the role of intrinsic airway neurons in airway hyperresponsiveness (AHR) induced by IL-1␤. Ferrets were instilled intratracheally with IL-1␤ (0.3 g/0.3 ml) or saline (0.3 ml) once daily for 5 days. Tracheal smooth muscle contractility in vitro and substance P (SP) expression in tracheal neurons were assessed. Tracheal smooth muscle reactivity to acetylcholine (ACh) and methacholine (MCh) and smooth muscle contractions to electric field stimulation (EFS) both increased after IL-1␤. The IL-1␤-induced AHR was maintained in tracheal segments cultured for 24 h, a procedure that depletes SP from sensory nerves while maintaining viability of intrinsic airway neurons. Pretreatment with CP-99994, an antagonist of neurokinin 1 receptor, attenuated the IL-1␤-induced hyperreactivity to ACh and MCh and to EFS in cultured tracheal segments. SP-containing neurons in longitudinal trunk, SP innervation of superficial muscular plexus neurons, and SP nerve fiber density in tracheal smooth muscle all increased after treatment with IL-1␤. These results show that IL-1␤-enhanced cholinergic airway smooth muscle contractile responses are mediated by the actions of SP released from intrinsic airway neurons. airway inflammation; airway smooth muscle contraction; muscarinic agonists; neurokinin receptor; airway innervation

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“…Thus, by 1993, intrinsic neurons containing VIP, SP and NOS were known to be present in the airways. Intrinsic airway neurons expressing VIP, SP or NOS have been studied in rats (Fontan, Cortright et al 2000;Van Genechten, Brouns et al 2003), cats (Dey and Zhu 1993), guinea pigs (Fischer, Canning et al 1996), ferrets (Dey, Mayer et al 1993;Dey, Altemus et al 1996;Wu, Maize et al 2001;Wu and Dey 2006), and humans (Fischer, Canning et al 1996). No studies of VIP-expressing intrinsic airway neurons have been carried out in pigs, in spite of the extensive use of pigs as models of human airway function.…”

Section: Airway Intrinsic Neurons Expressing Vip Nos and Spmentioning

confidence: 99%

Parasympathetic control of airway submucosal glands: Central reflexes and the airway intrinsic nervous system

Wine

2007

Autonomic Neuroscience

100

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Airway submucosal glands produce the mucus that lines the upper airways to protect them against insults. This review summarizes evidence for two forms of gland secretion, and hypothesizes that each is mediated by different but partially overlapping neural pathways. Airway innate defense comprises low level gland secretion, mucociliary clearance and surveillance by airway-resident phagocytes to keep the airways sterile in spite of nearly continuous inhalation of low levels of pathogens. Gland secretion serving innate defense is hypothesized to be under the control of intrinsic (peripheral) airway neurons and local reflexes, and these may depend disproportionately on noncholinergic mechanisms, with most secretion being produced by VIP and tachykinins. In the genetic disease cystic fibrosis, airway glands no longer secrete in response to VIP alone and fail to show the synergy between VIP, tachykinins and ACh that is observed in normal glands. The consequent crippling of the submucosal gland contribution to innate defense may be one reason that cystic fibrosis airways are infected by mucus-resident bacteria and fungi that are routinely cleared from normal airways. By contrast, the acute (emergency) airway defense reflex is centrally mediated by vagal pathways, is primarily cholinergic, and stimulates copious volumes of gland mucus in response to acute, intense challenges to the airways, such as those produced by very vigorous exercise or aspiration of foreign material. In cystic fibrosis, the acute airway defense reflex can still stimulate the glands to secrete large amounts of mucus, although its properties are altered. Importantly, treatments that recruit components of the acute reflex, such as inhalation of hypertonic saline, are beneficial in treating cystic fibrosis airway disease. The situation for recipients of lung transplants is the reverse; transplanted airways retain the airway intrinsic nervous system but lose centrally mediated reflexes. The consequences of this for gland secretion and airway defense are poorly understood, but it is possible that interventions to modify submucosal gland secretion in transplanted lungs might have therapeutic consequences.

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Role of intrinsic airway neurons in ozone-induced airway hyperresponsiveness in ferret trachea

Cited by 23 publications

References 39 publications

Sensory Neural Responses to Ozone Exposure during Early Postnatal Development in Rat Airways

Sensory Neural Responses to Ozone Exposure during Early Postnatal Development in Rat Airways

Interleukin-1β-induced airway hyperresponsiveness enhances substance P in intrinsic neurons of ferret airway

Parasympathetic control of airway submucosal glands: Central reflexes and the airway intrinsic nervous system

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