Cyclic GMP and Cilia Motility

Wyatt, Todd A.

doi:10.3390/cells4030315

Cited by 20 publications

(11 citation statements)

References 86 publications

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“…However, the identification of factors that enhance CBF have been useful for the development of therapies to improve MCC in patients with chronic airway diseases. For example, CBF can be stimulated by β-adrenergic agonists (Bennett 2002), intracellular increase of nucleotides, including cAMP and cGMP (Satir and Sleigh 1990; Wanner et al 1996; Wyatt 2015) and an intracellular increase of Ca +2 . Ciliated cells express multiple bitter taste receptors (R2T) that localize at different places along the cilium, making it a chemosensory organelle.…”

Section: Role Of Airway Cilia In MCC and Its Regulationmentioning

confidence: 99%

Cilia and Mucociliary Clearance

Bustamante-Marin

Ostrowski

2016

Cold Spring Harb Perspect Biol

561

409

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Mucociliary clearance (MCC) is the primary innate defense mechanism of the lung. The functional components are the protective mucous layer, the airway surface liquid layer, and the cilia on the surface of ciliated cells. The cilia are specialized organelles that beat in metachronal waves to propel pathogens and inhaled particles trapped in the mucous layer out of the airways. In health this clearance mechanism is effective, but in patients with primary cilia dyskinesia (PCD) the cilia are abnormal, resulting in deficient MCC and chronic lung disease. This demonstrates the critical importance of the cilia for human health. In this chapter we summarize the current knowledge of the components of the MCC apparatus, focusing on the role of cilia in MCC.

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Section: Role Of Airway Cilia In MCC and Its Regulationmentioning

confidence: 99%

Cilia and Mucociliary Clearance

Bustamante-Marin

Ostrowski

2016

Cold Spring Harb Perspect Biol

561

409

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“…Moreover, the advent of e-cigarettes and other nicotine “vaping” devices has led to the commercial promotion of these products as having reduced risk for adverse health effects associated with tobacco products. In addition to published studies pointing to dysmorphology and dysfunction of mucociliary clearance mechanisms associated with tobacco smoke exposure, there is a growing awareness of the role of the regulation of ciliary function modulation by nitric oxide (NO) (Jain et al, 1993; Jiao et al, 2011; Maniscalco et al, 2016; Ostrowski et al, 2012; Sisson et al, 2009; Vleeming et al, 2002; Wyatt, 2015; Zhou et al, 2009, 2011). While a variety of agents such as alcohol, tobacco smoke and microbiological products have been shown to affect this mechanism, there is little data to inform how NO modulation of ciliary function might be associated with e-cigarette use (Hariri et al, 2016; Sisson et al, 2009; Zhou et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Temporal structure/function variation in cultured differentiated human nasal epithelium associated with acute single exposure to tobacco smoke or E-cigarette vapor

Carson

Zhou

Brighton

et al. 2017

Inhalation Toxicology

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Objective Mucociliary clearance sustains a baseline functionality and an “on demand” capability to upregulate clearance upon irritant exposure involving mucus hypersecretion and accelerated ciliary beat frequency (CBF) modulated by nitric oxide (NO). This study characterized these elements as well as cellular and exogenous NO concentrations subsequent to a single exposure to tobacco smoke (TS) or e-cigarette vapor (EV) on cultured human airway epithelium. Materials and methods Air-liquid interface (ALI) airway epithelial cultures per nonsmoking human subjects were subjected to single TS or EV exposures. Measures of ciliary function and secretion were performed and cellular and exogenous NO concentrations under control and experimental conditions were assessed. Results Both TS and EV exposures resulted similar patterns of decline in CBF within 1 min of the completion of exposure followed by a gradual return often exceeding baseline within 1 h. Post-exposure examination of exposed cultures suggested morphologic differences in secretory function relative to controls. The relative NO concentrations of TS and EV chamber air were sharply different with EV NO being only slightly elevated relative to cellular NO production. Discussion and conclusions Epithelial remodeling and mucociliary dysfunction have been clearly associated with TS exposure. However, information contrasting epithelial structure/function following a single acute TS or EV exposure is limited. This study demonstrates a similar pattern of epithelial response to acute TS or EV exposure. Inasmuch as NO may contribute to an inflammatory milieu and generation of toxic metabolites, it is plausible that recurrent exposures over time may be contributory to chronic pathologies.

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“…cGMP may activate cGMP-dependent kinase (PKG) and, potentially, cAMP-dependent protein kinase (PKA) (Lorenz et al, 2017), which in turn may phosphorylate dyneins or kinesins of the axoneme, altering the cilia beating. PKG has been detected in the axonemes of the tracheal cilia; moreover, in isolated cilia preparations submicromolar concentrations of cGMP induced phosphorylation of the ciliary proteins (Gertsberg et al, 2004;Wyatt, 2015).…”

Section: Discussionmentioning

confidence: 99%

nNOS regulates ciliated cell polarity, ciliary beat frequency, and directional flow in mouse trachea

et al. 2021

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Clearance of the airway is dependent on directional mucus flow across the mucociliary epithelium, and deficient flow is implicated in a range of human disorders. Efficient flow relies on proper polarization of the multiciliated cells and sufficient ciliary beat frequency. We show that NO, produced by nNOS in the multiciliated cells of the mouse trachea, controls both the planar polarity and the ciliary beat frequency and is thereby necessary for the generation of the robust flow. The effect of nNOS on the polarity of ciliated cells relies on its interactions with the apical networks of actin and microtubules and involves RhoA activation. The action of nNOS on the beat frequency is mediated by guanylate cyclase; both NO donors and cGMP can augment fluid flow in the trachea and rescue the deficient flow in nNOS mutants. Our results link insufficient availability of NO in ciliated cells to defects in flow and ciliary activity and may thereby explain the low levels of exhaled NO in ciliopathies.

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Cyclic GMP and Cilia Motility

Cited by 20 publications

References 86 publications

Cilia and Mucociliary Clearance

Cilia and Mucociliary Clearance

Temporal structure/function variation in cultured differentiated human nasal epithelium associated with acute single exposure to tobacco smoke or E-cigarette vapor

nNOS regulates ciliated cell polarity, ciliary beat frequency, and directional flow in mouse trachea

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