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

2021 ◽  
Vol 4 (5) ◽  
pp. e202000981
Author(s):  
Anatoly Mikhailik ◽  
Tatyana V Michurina ◽  
Krikor Dikranian ◽  
Stephen Hearn ◽  
Vladimir I Maxakov ◽  
...  
Keyword(s):  
Beat Frequency ◽  
Ciliated Cell ◽  
Ciliary Beat Frequency ◽  
Ciliary Activity ◽  
Ciliated Cells ◽  
No Donors ◽  
Multiciliated Cells ◽  
Human Disorders ◽  
Low Levels ◽  
Ciliary Beat

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.

Functional cross talk after activation of P2 and P1 receptors in oviductal ciliated cells

2000 ◽  
Vol 279 (3) ◽  
pp. C658-C669 ◽  
Author(s):  
Bernardo Morales ◽  
Nelson Barrera ◽  
Pablo Uribe ◽  
Claudio Mora ◽  
Manuel Villalón
Keyword(s):  
Cross Talk ◽  
Adenosine Receptors ◽  
Beat Frequency ◽  
Ciliated Cell ◽  
Ciliary Beat Frequency ◽  
Ciliary Activity ◽  
Dependent Manner ◽  
Ciliated Cells ◽  
P1 Receptors ◽  
Intracellular Ca

The presence of ATP and adenosine receptors and their role in controlling ciliary activity in oviductal ciliated cells was studied by measuring the ciliary beat frequency (CBF) in oviductal tissue cultures. ATP, adenosine, and related compounds increased the CBF in a dose-dependent manner. We established that P2 receptors of subtype 2Y2 and P1 receptors of subtype A2a mediated the responses to ATP and adenosine, respectively. We found evidence to suggest that stimulation of ciliary activity by ATP requires d- myo-inositol 1,4,5-trisphosphate [Ins(1,4,5) P 3] metabolism, intracellular Ca2+ mobilization, and protein kinase C activation. On the other hand, the adenosine effect is mediated by activation of a Gs protein-dependent pathway that enhances cAMP intracellular levels. To study the interaction between P2 and P1 receptors, cells were stimulated simultaneously with both agonists. We observed a synergistic increase of the CBF even at agonist concentrations (100 nM) that did not produce a significant response when added separately to the culture. Furthermore, a blocker of the cAMP pathway produced a reduction of the ATP response, whereas a blocker of the Ins(1,4,5) P 3 pathway also produced an inhibition of the adenosine response. Our evidence demonstrates that both ATP and adenosine receptors are present in a single ciliated cell and that a mechanism of cross talk could operate in the transduction pathways to control ciliary activity.

Early Mucosal Changes in Experimental Sinusitis

1992 ◽  
Vol 107 (4) ◽  
pp. 537-548 ◽  
Author(s):  
Michael L. Hinni ◽  
Thomas V. Mccaffrey ◽  
Jan L. Kasperbauer
Keyword(s):  
Defense Mechanism ◽  
Beat Frequency ◽  
Acute Infection ◽  
Ciliated Cell ◽  
Ciliary Beat Frequency ◽  
Acute Sinusitis ◽  
Ciliated Cells ◽  
Predisposing Factor ◽  
Sinus Mucosa ◽  
Ciliary Beat

Normal mucociliary flow is a significant defense mechanism in the prevention of acute sinusitis. We have undertaken a study to examine the early sinus mucosal and mucociliary changes that occur in response to acute infection. Twenty rabbits were evaluated for 5 days after an obstructed maxillary sinus was inoculated with either Streptococcus pneumoniae, Hemophilus influenzae, Pseudomonas aeruginosa, or a sterile saline solution. Data collected included measurements of sinus mucosal ciliary beat frequency, quantitation of ciliated cell losses, and electron microscopic observations. Results demonstrate statistically significant (p < 0.05) changes in mucosal ciliary beat frequency that were either excitatory or inhibitory, depending both on the length of the infection and the specific organism. No changes in ciliary beat frequency were observed in the control animals (p > 0.55). Control animals likewise demonstrated no loss of ciliated cells from mucosal epithelium; however, dramatic losses of ciliated cells from the sinus mucosa of the experimental groups were observed. These losses occurred at different rates, depending on the infecting organism, but all infected groups demonstrated a >86% decrease in the number of viable ciliated cells from the sinus mucosa after sinusitis of 5 days duration. We conclude that a significant loss of ciliated cells from sinus mucosa and a corresponding disruption of normal mucociliary flow occurs early after exposure to pathogenic organisms and is a significant predisposing factor in the development of acute sinusitis.

scholarly journals Ciliomotor circuitry underlying whole-body coordination of ciliary activity in the Platynereis larva

2017 ◽  
Author(s):  
Csaba Verasztó ◽  
Nobuo Ueda ◽  
Luis A. Bezares-Calderón ◽  
Aurora Panzera ◽  
Elizabeth A. Williams ◽  
...  
Keyword(s):  
Beat Frequency ◽  
Ciliary Beat Frequency ◽  
Whole Body ◽  
Ciliary Activity ◽  
Ciliary Beating ◽  
Stop And Go ◽  
Multiciliated Cells ◽  
Platynereis Dumerilii ◽  
Catecholaminergic Cells ◽  
Ciliary Locomotion

AbstractCiliated surfaces harbouring synchronously beating cilia can generate fluid flow or drive locomotion. In ciliary swimmers, ciliary beating, arrests, and changes in beat frequency are often coordinated across extended or discontinuous surfaces. To understand how such coordination is achieved, we studied the ciliated larvae of Platynereis dumerilii, a marine annelid. Platynereis larvae have segmental multiciliated cells that regularly display spontaneous coordinated ciliary arrests. We used whole-body connectomics, activity imaging, transgenesis, and neuron ablation to characterize the ciliomotor circuitry. We identified cholinergic, serotonergic, and catecholaminergic ciliomotor neurons. The synchronous rhythmic activation of cholinergic cells drives the coordinated arrests of all cilia. The serotonergic cells are active when cilia are beating. Serotonin inhibits the cholinergic rhythm, and increases ciliary beat frequency. Based on their connectivity and alternating activity, the catecholaminergic cells may generate the rhythm. The ciliomotor circuitry thus constitutes a stop-and-go pacemaker system for the whole-body coordination of ciliary locomotion.

Control of the beat cycle of respiratory tract cilia by Ca2+ and cAMP

1992 ◽  
Vol 263 (2) ◽  
pp. L232-L242 ◽  
Author(s):  
A. B. Lansley ◽  
M. J. Sanderson ◽  
E. R. Dirksen
Keyword(s):  
Respiratory Tract ◽  
Beat Frequency ◽  
Ciliary Beat Frequency ◽  
Ciliated Cells ◽  
Intact Cells ◽  
Permeabilized Cells ◽  
Whole Cells ◽  
Phase Reduction ◽  
Before And After ◽  
Ciliary Beat

Beat frequency and the duration of the constituent recovery, effective, and rest phases of the beat cycle of respiratory tract cilia were measured photoelectronically before and after manipulation with ionomycin or isoproterenol. Both ionomycin, acting by increasing intracellular Ca2+, and isoproterenol, acting by elevating intracellular adenosine 3',5'-cyclic monophosphate (cAMP), increased beat frequency by reducing the duration of the three phases of the ciliary beat cycle in a similar manner. The addition of increasing concentrations of ATP to ciliated cells permeabilized by exposure to saponin caused a pattern of phase reduction indistinguishable from that observed in whole cells. The beat frequency of permeabilized cells was slower than that of whole cells and insensitive to changes in Ca2+ and cAMP. Ca2+ and cAMP may regulate ciliary beat frequency by acting at a common site within intact cells, possibly regulating the rate at which the axoneme can use ATP or the availability of ATP to the axoneme.

Honorable Mention — Student Research Award 1995: Signal Transduction Mechanisms in Substance P-Mediated Ciliostimulation

1995 ◽  
Vol 113 (5) ◽  
pp. 582-588 ◽  
Author(s):  
Rodney J. Schlosser ◽  
Judith M. Czaja ◽  
Thomas V. McCaffrey
Keyword(s):  
Nitric Oxide ◽  
Substance P ◽  
Beat Frequency ◽  
Ciliary Beat Frequency ◽  
Ciliary Activity ◽  
Intermediate Step ◽  
Nitric Oxide Production ◽  
Oxide Production ◽  
Vitro Effect ◽  
Ciliary Beat

Substance P is a neuropeptide released by afferent neurons in the respiratory tract during inflammatory reactions. It produces effects on blood vessels, bronchial smooth muscle, nasal glands, and respiratory cilia. We studied the in vitro effect of substance P on the ciliary beat frequency of human adenoid explants and its mechanism of action. Substance P was added to cultured adenoid at concentrations of 10−10, 10−8, 10−6, and 10−4 mol/L. Ciliary beat frequency was determined with phase-contrast microscopy and microphotometry. Substance P increased ciliary beat frequency a maximum of 11.9% ± 3.8% ( p < 0.01). Diclofenac (10−6 mol/L) significantly blocked the ciliostimulatory effects of SP ( p < 0.022), indicating that prostaglandin synthesis is an intermediate step in the action of substance P on ciliary beat frequency. The L-arginine analogs, NG-nitro-L-arginine methyl ester and NG-monomethyl-L-arginine, inhibit nitric oxide synthesis from L-arginine. L-Arginine analogs (10−4 to 10−2 mol/L) inhibited the effect of substance P ( p < 0.02 at the higher concentration). This inhibition was reversed by adding L-arginine, demonstrating that nitric oxide production is a required step in substance P-induced ciliostimulation. Substance P stimulates ciliary activity in human nasal mucosa as a result of secondary production and release of endogenous prostaglandins and nitric oxide. It is likely that inflammatory disease processes that stimulate release of substance P and subsequent prostaglandin and nitric oxide production modify mucociliary transport. Pharmacologic modification of substance P and its second messengers may eventually permit regulation of this important defense mechanism and control of neurogenic inflammation.

Experience in Counting Ciliary Beat Frequency from Vital Cytologic Sampling

1989 ◽  
Vol 3 (3) ◽  
pp. 151-154
Author(s):  
T. Deitmer ◽  
S. Phadhana-anek
Keyword(s):  
Functional State ◽  
Beat Frequency ◽  
Ciliary Beat Frequency ◽  
Time Shift ◽  
Ciliated Cells ◽  
Good Picture ◽  
Brush Biopsy ◽  
Epithelial Cell Layer ◽  
Sampling Procedures ◽  
Ciliary Beat

From a viable cytologic brush biopsy of the respiratory epithelium you can get an insight into the functional state of the epithelial cell layer, especially of the ciliated cells. We report on our experience of several hundred sampling procedures from the nasal and bronchial mucosa. The technique of the method is described, including the microphotometric apparatus to determine the ciliary beat frequency. We stress the importance of checking the ciliary beat frequency of the 10 most active cells of one preparation to get representative results. Futhermore it is decisive to watch them over a period of 10 seconds, considering the time shift of the ciliary beat frequency. Putting the cell solution into a counting chamber gives the possibility of differentiating viable and dead ciliated cells as well as squamous cells in the sample. These results proved to yield a good picture of the functional state of the sampled respiratory mucosal site.

scholarly journals TNFαAffects Ciliary Beat Response to Increased Viscosity in Human Pediatric Airway Epithelium

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Claudia González ◽  
Karla Droguett ◽  
Mariana Rios ◽  
Noam A. Cohen ◽  
Manuel Villalón
Keyword(s):  
Airway Epithelium ◽  
Beat Frequency ◽  
Ciliary Beat Frequency ◽  
Ciliated Cells ◽  
Upper Airways ◽  
Pediatric Airway ◽  
Adenoid Tissue ◽  
Before And After ◽  
Autoregulatory Mechanism ◽  
Ciliary Beat

In airway epithelium, mucociliary clearance (MCC) velocity depends on the ciliary beat frequency (CBF), and it is affected by mucus viscoelastic properties. Local inflammation induces secretion of cytokines (TNFα) that can alter mucus viscosity; however airway ciliated cells have an autoregulatory mechanism to prevent the collapse of CBF in response to increase in mucus viscosity, mechanism that is associated with an increment in intracellular Ca+2level (Ca2+i). We studied the effect of TNFαon the autoregulatory mechanism that regulates CBF in response to increased viscosity using dextran solutions, in ciliated cells cultured from human pediatric epithelial adenoid tissue. Cultures were treated with TNFα, before and after the viscous load was changed. TNFαtreatment produced a significantly larger decrease in CBF in cultures exposed to dextran. Furthermore, an increment inCa2+iwas observed, which was significantly larger after TNFαtreatment. In conclusion, although TNFαhas deleterious effects on ciliated cells in response to maintaining CBF after increasing viscous loading, it has a positive effect, since increasingCa2+imay prevent the MCC collapse. These findings suggest that augmented levels of TNFαassociated with an inflammatory response of the nasopharyngeal epithelium may have dual effects that contribute to maintaining the effectiveness of MCC in the upper airways.

scholarly journals Ciliomotor circuitry underlying whole-body coordination of ciliary activity in the Platynereis larva

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Csaba Verasztó ◽  
Nobuo Ueda ◽  
Luis A Bezares-Calderón ◽  
Aurora Panzera ◽  
Elizabeth A Williams ◽  
...  
Keyword(s):  
Beat Frequency ◽  
Ciliary Beat Frequency ◽  
Whole Body ◽  
Ciliary Activity ◽  
Ciliary Beating ◽  
Stop And Go ◽  
Multiciliated Cells ◽  
Platynereis Dumerilii ◽  
Catecholaminergic Cells ◽  
Ciliary Locomotion

Ciliated surfaces harbouring synchronously beating cilia can generate fluid flow or drive locomotion. In ciliary swimmers, ciliary beating, arrests, and changes in beat frequency are often coordinated across extended or discontinuous surfaces. To understand how such coordination is achieved, we studied the ciliated larvae of Platynereis dumerilii, a marine annelid. Platynereis larvae have segmental multiciliated cells that regularly display spontaneous coordinated ciliary arrests. We used whole-body connectomics, activity imaging, transgenesis, and neuron ablation to characterize the ciliomotor circuitry. We identified cholinergic, serotonergic, and catecholaminergic ciliomotor neurons. The synchronous rhythmic activation of cholinergic cells drives the coordinated arrests of all cilia. The serotonergic cells are active when cilia are beating. Serotonin inhibits the cholinergic rhythm, and increases ciliary beat frequency. Based on their connectivity and alternating activity, the catecholaminergic cells may generate the rhythm. The ciliomotor circuitry thus constitutes a stop-and-go pacemaker system for the whole-body coordination of ciliary locomotion.

scholarly journals PKA induces Ca2+ release and enhances ciliary beat frequency in a Ca2+-dependent and -independent manner

1998 ◽  
Vol 275 (3) ◽  
pp. C790-C797 ◽  
Author(s):  
Alex Braiman ◽  
Orna Zagoory ◽  
Zvi Priel
Keyword(s):  
Beat Frequency ◽  
Ciliary Beat Frequency ◽  
Ciliary Activity ◽  
Experimental Conditions ◽  
Independent Manner ◽  
Ciliary Beating ◽  
Independent Mechanism ◽  
Intracellular Ca ◽  
Ciliary Beat

The intent of this work was to evaluate the role of cAMP in regulation of ciliary activity in frog mucociliary epithelium and to examine the possibility of cross talk between the cAMP- and Ca2+-dependent pathways in that regulation. Forskolin and dibutyryl cAMP induced strong transient intracellular Ca2+ concentration ([Ca2+]i) elevation and strong ciliary beat frequency enhancement with prolonged stabilization at an elevated plateau. The response was not affected by reduction of extracellular Ca2+concentration. The elevation in [Ca2+]iwas canceled by pretreatment with 1,2-bis(2-aminophenoxy)ethane- N, N, N′, N′-tetraacetic acid-AM, thapsigargin, and a phospholipase C inhibitor, U-73122. Under those experimental conditions, forskolin raised the beat frequency to a moderately elevated plateau, whereas the initial strong rise in frequency was completely abolished. All effects were canceled by H-89, a selective protein kinase A (PKA) inhibitor. The results suggest a dual role for PKA in ciliary regulation. PKA releases Ca2+ from intracellular stores, strongly activating ciliary beating, and, concurrently, produces moderate prolonged enhancement of the beat frequency by a Ca2+-independent mechanism.

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