Substance P and Ciliary Beat of Human Upper Respiratory Cilia in Vitro

1995 ◽  
Vol 104 (10) ◽  
pp. 798-802 ◽  
Author(s):  
Paul J. Schuil ◽  
Maartje Ten Berge ◽  
Kees Graamans ◽  
José M. E. Van Gelder ◽  
Egbert H. Huizing
Keyword(s):  
Substance P ◽  
Beat Frequency ◽  
Ciliary Beat Frequency ◽  
Computer Assisted ◽  
Ciliary Activity ◽  
Upper Respiratory Tract ◽  
Upper Respiratory ◽  
Ciliary Beat

On stimulation of trigeminal nerve endings, neuropeptides are released into the nasal mucosa. Among these neuropeptides is substance P (SP). In this study, we determined the effect in vitro of SP, as well as SP together with thiorphan, a blocker of the SP-degrading enzyme neutral endopeptidase, on the ciliary beat frequency (CBF) of the human upper respiratory tract. Ciliated epithelium of human adenoid tissue was used in the experiments. The CBF was measured by means of a computer-assisted photoelectric method. Substance P (10−8 to 10−5 mol/L, n = 7) showed a small but statistically significant dose-dependent decrease in CBF. On perfusion with SP (10−8 to 10−5 mol/L, n = 8) in combination with thiorphan, no statistically significant effect was found. We conclude that SP does not have a direct effect on ciliary activity to such an extent that it will affect mucociliary transport in vivo.

Stimulation of ciliary beat frequency by autonomic agonists: in vivo

1988 ◽  
Vol 65 (2) ◽  
pp. 971-981 ◽  
Author(s):  
L. B. Wong ◽  
I. F. Miller ◽  
D. B. Yeates
Keyword(s):  
Beat Frequency ◽  
Ciliary Beat Frequency ◽  
Ciliary Activity ◽  
Base Line ◽  
Muscarinic Cholinergic ◽  
The Mean ◽  
Beta 2 ◽  
Ciliary Beat

beta 2-Adrenergic bronchodilator and muscarinic cholinergic bronchoconstrictor agonists both stimulate ciliary activity in vitro. To test the hypothesis that increases in autonomic activity would result in increases in ciliary beat frequency (CBF) in vivo, a correlation analysis heterodyne laser light-scattering system was developed and validated to measure the stimulating effects of sympathomimetic and parasympathomimetic agonists on tracheal CBF in intact, anesthetized beagles. The mean baseline CBF from 42 studies of 274 measurements in 9 (5 male and 4 female) adult beagles was 6.6 +/- 1.1 Hz. The stimulating effects of a beta 2-adrenergic agonist, fenoterol, and a muscarinic cholinergic agonist, methacholine, on CBF were studied on four and eight beagles, respectively. The studies were randomized and blinded. Aerosolized 10(-5) M fenoterol stimulated the CBF from the base line of 6.8 +/- 2.5 to 32.0 +/- 17.9 Hz in four dogs. Aerosolized methacholine stimulated the CBF from the base line of 5.8 +/- 0.7 to 9.4 +/- 3.0 Hz for 10(-8) M, and to 12.6 +/- 3.1 Hz for 10(-6) M in eight dogs. These are the first data obtained in intact animals that demonstrate CBF in the lower respiratory tract is regulated by autonomic agonists.

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.

Leukotrienes C4 and D4 Increase the Ciliary Beat Frequency in Human Upper Airway Mucosa in Vitro

1998 ◽  
Vol 118 (4) ◽  
pp. 472-477 ◽  
Author(s):  
Carlos B. Cyrus ◽  
Bin Yang ◽  
Thomas V. McCaffrey
Keyword(s):  
Beat Frequency ◽  
Upper Airway ◽  
Ciliary Beat Frequency ◽  
Airway Mucosa ◽  
Contrast Microscopy ◽  
Leukotriene Receptor ◽  
Upper Respiratory ◽  
In Vitro Effects ◽  
Ciliary Beat

It has been suggested that leukotrienes C4 (LTC4) and D4 (LTD4) released from upper respiratory mucosa influence mucociliary transport during allergic reactions. We studied the in vitro effects of leukotrienes C4 and D4 on the ciliary beat frequency (CBF) of human adenoid explants over a 5-hour period. Tissue explants were cultured at 35° C in Minimum Essential Medium Eagle (MEM). The CBF was measured using phase contrast microscopy and microphotometry. Measurements of CBF were recorded in medium alone and in medium containing LTC4 or LTD4 at concentrations of 10−8 and 10−6 M. LTC4 and LTD4 increased CBF at concentrations of 10−8 and 10−6 M with increases of 20.51% ± 2.69% and 29.84% ± 4.06%, respectively. To determine the specificity of the LTC4 and LTD4 effects, the ciliated epithelium was treated with the specific leukotriene receptor antagonist LY-171,883 before administration of LTC4 and LTD4. LY-171,883 (10−6 M) significantly inhibited the ciliostimulatory effects of both leukotrienes. Our findings indicate that LTC4 and LTD4 increase CBF in vitro by activation of the LTD4 receptor.

Effect of Substance P on Ciliary Beat Frequency in Human Adenoid Explants

1992 ◽  
Vol 107 (4) ◽  
pp. 553-557 ◽  
Author(s):  
Paul A. Staskowski ◽  
Thomas V. Mccaffrey
Keyword(s):  
Substance P ◽  
Culture Media ◽  
Beat Frequency ◽  
Upper Airway ◽  
Ciliary Beat Frequency ◽  
Fast Fourier Transformation ◽  
Protective Mechanism ◽  
Ciliary Activity ◽  
Dependent Manner ◽  
Ciliary Beat

This study investigated the direct effects of substance P (SP) on ciliary beat frequency of human upper airway mucosa. Human adenoid explant tissue was maintained in serum free culture media, MCDB153. Ciliated epithelial cells were observed with phase-contrast microscopy and ciliary activity was measured using a photometric technique. Oscillations in transmitted light caused by ciliary beating were recorded and modal ciliary beat frequency was determined by fast Fourier transformation. Specimens were treated with SP at concentrations of 10−4, 10−5, 10−6, and 10−7 mol/L and with equal molar solutions of SP and (D-Pro2, D-Trp7,9)-SP, a SP antagonist. Substance P was found to increase ciliary beat frequency in a dose-dependent manner with a maximum increase of 12.1%. This effect was not seen with solutions containing (D-Pro2, D-Trp7,9)-SP. This suggests that SP exerts a direct stimulatory effect on ciliated cells of the upper airway. Because SP is known to be released in the upper airway in response to chemical irritation, it is presumed that the stimulatory effect of SP on mucosal cells provides a protective mechanism against inhaled irritants.

Modulation of Ciliary Beat Frequency in the Upper Airway by Prostaglandins

1996 ◽  
Vol 10 (4) ◽  
pp. 229-234 ◽  
Author(s):  
Rodney J. Schlosser ◽  
Ramon A. Franco ◽  
Judith M. Czaja ◽  
Thomas V. McCaffrey
Keyword(s):  
Culture Media ◽  
Beat Frequency ◽  
Upper Airway ◽  
Ciliary Beat Frequency ◽  
Prostaglandin E ◽  
Ciliary Activity ◽  
Maximum Increase ◽  
Endogenous Prostaglandins ◽  
Ciliary Beat

Prostaglandins are ubiquitous within tissues and participate in several local regulatory functions. Previous reports have presented conflicting evidence on their role in ciliary activity in the upper airway. We studied the in vitro effects of prostaglandin E2 (PGE2) and a prostaglandin I2 analog (Iloprost) on the ciliary beat frequency (CBF) of human adenoid explants and rabbit sinus mucosa. Tissue explants were maintained in culture at 35°C. PGE2 or Iloprost was added to the culture media at concentrations of 10–6, to 10–12 M. CBF was determined using phase contrast microscopy and microphotometry. PGE2 increased CBF with a maximum increase of 54.6% in rabbit mucosa (P < 0.01) and 20.0% in human adenoid (P < 0.009). Iloprost increased CBF with a maximum increase of 35.2% in rabbit mucosa (P < 0.02) and 16.4% in human adenoid (P < 0.03). Induced production of endogenous prostaglandins was determined by treating specimens with a cyclooxygenase inhibitor (diclofenac) prior to addition of PGE2 or Iloprost. Diclofenac had no effect on the ciliostimulatory effects of PGE2 (P > 0.36), however it significantly decreased the ciliostimulatory effect of Iloprost (P < 0.037). Both PGE2 and Iloprost stimulate ciliary motility, yet the action of PGE2 is direct, whereas Iloprost stimulates cilia by release of endogenous prostaglandins in both the human and rabbit.

Muscarinic Ciliostimulation Requires Endogenous Prostaglandin Production

1998 ◽  
Vol 12 (3) ◽  
pp. 203-208 ◽  
Author(s):  
Scott M. Gayner ◽  
Thomas V. McCaffrey
Keyword(s):  
Phospholipase A2 ◽  
Phospholipase C ◽  
Beat Frequency ◽  
Ciliary Beat Frequency ◽  
Pge2 Production ◽  
Ciliary Activity ◽  
Frequency Increase ◽  
Prostaglandin Production ◽  
Ciliary Beat

Prostaglandin E2 (PGE2) is a known modulator in upper airway ciliary activity and may be involved in the transduction of the muscarinic acetylcholine receptor signal. We studied the in vitro effects of muscarinic ciliostimulation on ciliary beat frequency (CBF) and PGE2 in human adenoid explants to determine whether PGE2 production is an essential step in the signal transduction mechanism. Methacholine applied to adenoid explants significantly increased ciliary beat frequency. This effect was blocked by the application of diclofenac, a cyclooxygenase inhibitor. Using radioimmunoassay, PGE2 production was measured during ciliostimulation with methacholine. Methacholine produced a significant increase in production in PGE2 during ciliostimulation. The roles of phospholipase C and phospholipase A2 in prostaglandin production were investigated by inhibiting these enzymes. D609, a phospholipase C inhibitor, significantly inhibited ciliary beat frequency increase and PGE2 production during methacholine stimulation. However, PACOCF3, a phospholipase A2 inhibitor, did not block ciliary beat frequency increase or PGE2 production in response to methacholine. These data show that phospholipase C is required for PGE2 production and ciliostimulation.

Histamine and leukotriene C4 effects on in vitro ciliary beat frequency of human upper respiratory cilia

1994 ◽  
Vol 251 (6) ◽  
pp. 325-328 ◽  
Author(s):  
P. J. Schuil ◽  
J. M. E. van Gelder ◽  
M. ten Berge ◽  
K. Graamans ◽  
E. H. Huizing
Keyword(s):  
Beat Frequency ◽  
Ciliary Beat Frequency ◽  
Leukotriene C4 ◽  
Respiratory Cilia ◽  
Upper Respiratory ◽  
Ciliary Beat

Role of ciliary motility in acute allergic mucociliary dysfunction

1982 ◽  
Vol 52 (4) ◽  
pp. 1018-1023 ◽  
Author(s):  
D. R. Maurer ◽  
M. Sielczak ◽  
W. Oliver ◽  
W. M. Abraham ◽  
A. Wanner
Keyword(s):  
Beat Frequency ◽  
Slow Motion ◽  
Ciliary Beat Frequency ◽  
Ciliary Activity ◽  
Base Line ◽  
Conscious Sheep ◽  
Line P ◽  
Chemical Mediators

The purpose of this investigation was to determine if abnormal ciliary function contributes to allergic mucociliary dysfunction. In conscious sheep with Ascaris suum hypersensitivity, ciliated cells were obtained with a cytology brush and tracheal mucous velocity (TMV) was determined before and serially for 2 h following antigen inhalation. The recovered cells (also containing mast cells) were suspended in a chamber, and ciliary activity was viewed microscopically and recorded on videotape for subsequent slow-motion analysis of ciliary beat frequency (CBF). One hour after A. suum challenge mean CBF (+/- SE) showed a slight increase from a base-line value of 630 +/- 16 to 716 +/- 30 beats/min (P less than 0.05) when mean TMV was decreased to 57% of base line (P less than 0.05). After 2 h, both mean CBF and TMV returned toward base line. Since possible in vivo actions of chemical mediators liberated by antigen challenge may have been lost after suspension of the brushed cells, we also assessed the effects of antigen on CBF in vitro. A. suum caused a dose-dependent increase in CBF that was blocked by cromolyn sodium. We conclude that 1) allergic mucociliary dysfunction is not caused by a decrease in CBF and 2) antigen-induced release of chemical mediators increases CBF.

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