Proliferation and repair of guinea pig tracheal epithelium after neuropeptide depletion and injury in vivo

Kim, John S.; McKinnis, Valerie S.; Adams, Kate; White, Steven R.

doi:10.1152/ajplung.1997.273.6.l1235

Cited by 21 publications

(20 citation statements)

References 26 publications

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“…This effect is similar to the effect that substance P has on modulating the migration and proliferation of cells after the mechanical injury of tracheal epithelium (21). Substance P stimulates proliferation and migration of guinea pig tracheal epithelial cells (19), and works synergistically with insulin-like growth factor-1 to stimulate corneal epithelial wound healing (20,44).…”

Section: Discussionmentioning

confidence: 56%

“…In turn, NK-1 receptors have been shown to be present in numerous lung structures, including the airway epithelium from the bronchi to the alveoli of guinea pigs and humans (16,17). Substance P, via NK-1 receptors, plays a role in regulating airway blood flow, airway smooth muscle responses, airway inflammation (18), and epithelial migration and proliferation of cells, including tracheal epithelial cells, after injury (19)(20)(21). Substance P induces superoxide production in neutrophils, is a chemotactic agent for human neutrophils, and primes neutrophils for response to other activating agents (22)(23)(24).…”

mentioning

confidence: 99%

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Activation of Neurokinin-1 Receptors during Ozone Inhalation Contributes to Epithelial Injury and Repair

Oslund¹,

Hyde

Putney³

et al. 2008

Am J Respir Cell Mol Biol

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We investigated the importance of neurokinin (NK)-1 receptors in epithelial injury and repair and neutrophil function. Conscious Wistar rats were exposed to 1 ppm ozone or filtered air for 8 hours, followed by an 8-hour postexposure period. Before exposure, we administered either the NK-1 receptor antagonist, SR140333, or saline as a control. Ethidium homodimer was instilled into lungs as a marker of necrotic airway epithelial cells. After fixation, whole mounts of airway dissected lung lobes were immunostained for 5-bromo-29-deoxyuridine, a marker of epithelial proliferation. Both ethidium homodimer and 5-bromo-29-deoxyuridine-positive epithelial cells were quantified in specific airway generations. Rats treated with the NK-1 receptor antagonist had significantly reduced epithelial injury and epithelial proliferation compared with control rats. Sections of terminal bronchioles showed no significant difference in the number of neutrophils in airways between groups. In addition, staining ozone-exposed lung sections for active caspase 3 showed no apoptotic cells, but ethidium-positive cells colocalized with the orphan nuclear receptor, Nur77, a marker of nonapoptotic, programmed cell death mediated by the NK-1 receptor. An immortalized human airway epithelial cell line, human bronchial epithelial-1, showed no significant difference in the number of oxidant stresspositive cells during exposure to hydrogen peroxide and a range of SR140333 doses, demonstrating no antioxidant effect of the receptor antagonist. We conclude that activation of the NK-1 receptor during acute ozone inhalation contributes to epithelial injury and subsequent epithelial proliferation, a critical component of repair, but does not influence neutrophil emigration into airways.

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Section: Discussionmentioning

confidence: 56%

mentioning

confidence: 99%

Activation of Neurokinin-1 Receptors during Ozone Inhalation Contributes to Epithelial Injury and Repair

Oslund¹,

Hyde

Putney³

et al. 2008

Am J Respir Cell Mol Biol

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“…However, in the presence of acute epithelial injury, cell proliferation becomes a prominent feature of the repair response, at least in small-animal models [3][4][5][6]. Such models indicate that the key events are the ability of the cells bordering the lesion to dedifferentiate, flatten, and thereafter migrate towards the denuded area to restore the barrier function of the epithelium and set the stage for further proliferation and differentiation to regenerate the pseudostratified epithelium.…”

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confidence: 99%

Analysis of airway epithelial regeneration and repair following endobronchial brush biopsy in sheep

Yahaya

Baker

Tennant

et al. 2011

Experimental Lung Research

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Understanding the fundamental processes involved in repairing the airway wall following injury is fundamental to understanding the way in which these processes are perturbed during disease pathology. Indeed complex diseases such as asthma and chronic obstructive pulmonary disease (COPD) have at their core evidence of airway wall remodeling processes that play a crucial functional role in these diseases. The authors sought to understand the dynamic cellular events that occur during bronchial airway epithelial repair in sheep. The injury was induced by endobronchial brush biopsy (BBr), a process that causes epithelial débridement and induces a consequential repair process. In addition, the current experimental protocol allowed for the time-dependent changes in airway wall morphology to be studied both within and between animals. The initial débridement was followed by evidence of dedifferentiation in the intact epithelium at the wound margins, followed by proliferation of cells both within the epithelium and in the deeper wall structures, notably in association with the submucosal glands and smooth muscle bundles. Seven days after injury, although the airway wall was thickened at the site of damage, the epithelial layer was intact, with evidence of redifferentiation. These studies, in demonstrating broad agreement with previous studies in small animals, indicate the wider relevance of this system as a comparative model and should provide a solid basis upon which to further characterize the critical cellular and molecular interactions that underlie both effective restitution and pathological repair.

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“…Beyond its potent vasodilatory effect (11), CGRP has numerous other effects that would be expected to influence the maintenance and function of the lower respiratory tract in health and disease. CGRP has been shown to modulate substance P-induced inflammation (32) and increase ciliary beat frequency (41) and has the potential to play a role in airway repair by inducing epithelial proliferation and migration (26,38,47). In addition, CGRP has been shown to have several immunomodulatory effects.…”

mentioning

confidence: 99%

“…stance P-induced inflammation (32) and increase ciliary beat frequency (41) and has the potential to play a role in airway repair by inducing epithelial proliferation and migration (26,38,47). In addition, CGRP has been shown to have several immunomodulatory effects.…”

mentioning

confidence: 99%

Proximal airway mucous cells of ovalbumin-sensitized and -challenged Brown Norway rats accumulate the neuropeptide calcitonin gene-related peptide

Larson¹,

Plopper²,

Baker³

et al. 2004

American Journal of Physiology-Lung Cellular and Molecular Phys

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Mucous cell hypersecretion and increased neuropeptide production play a role in the exacerbation of symptoms associated with asthma. The source of these neuropeptides have been confined to the contributions of small afferent nerves or possibly neuroendocrine cells. We tested the hypothesis that repeated exposure to allergen would alter the sources and abundance of neuropeptides in airways. Right middle lobes from rats (8 wk old) exposed to 2.5% ovalbumin (OVA) for five episodes (30 min each) or filtered air were inflation fixed with paraformaldehyde. The lobes were dissected to expose the airway tree, permeabilized with DMSO, and incubated in antibody to rat calcitonin gene-related peptide (CGRP), followed with a fluorochrome-labeled second antibody. CGRP-positive structures were imaged via confocal microscopy. Airways were later embedded in plastic and sectioned for cell identification. In animals challenged with OVA, CGRP-positive cells, not neuroendocrine or neuronal in origin (confirmed by a lack of protein gene product 9.5 signal), were recorded along the axial path. In section, this fluorescent signal was localized to granules within epithelial cells. Alcian blue/periodic acid-Schiff staining of these same sections positively identify these cells as mucous cells. Mucous cells of animals not challenged with OVA were not positive for CGRP. We conclude that episodic allergen exposure results in the accumulation of CGRP within mucous cells, creating a new source for the release of this neuropeptide within the airway.

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Proliferation and repair of guinea pig tracheal epithelium after neuropeptide depletion and injury in vivo

Cited by 21 publications

References 26 publications

Activation of Neurokinin-1 Receptors during Ozone Inhalation Contributes to Epithelial Injury and Repair

Activation of Neurokinin-1 Receptors during Ozone Inhalation Contributes to Epithelial Injury and Repair

Analysis of airway epithelial regeneration and repair following endobronchial brush biopsy in sheep

Proximal airway mucous cells of ovalbumin-sensitized and -challenged Brown Norway rats accumulate the neuropeptide calcitonin gene-related peptide

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