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Cilia: activation coupled to mechanical stimulation by calcium influx.

Ciliated epithelial cells in the oviduct of Necturus maculosus were stimulated mechanically by brief dimpling with a microstylus. This treatment produlced a transient depolarization of the membrane, and a transient increase in the frequency of ciliary beating. The increase in frequency of ciliary beating was related to the concentration of extracellular calcium ion, decreasing with reductiotn in calcium. Addition of lanthanum was followed by a decrease in spontaneous ciliary aictivity and a hyperpolarization of the membrane. In the presence of lanthanum, the transietnt depolarization in response to mechanical stimulation had a shorter timte course, and the concomitant increase in ciliary frequency was greatly reduced. It is concluded that calciuml ions enter the cell as a result of mechanical stimulationi of the membrane, and that calcium influx leads to an increase in the frequency of ciliary activity.

Animals↗

Streptococcus pneumoniae-induced inhibition of rat ependymal cilia is attenuated by antipneumolysin antibody.

Ciliated ependymal cells line the ventricular surfaces and aqueducts of the brain. In ex vivo experiments, pneumolysin caused rapid inhibition of the ependymal ciliary beat frequency and caused ependymal cell disruption. Wild-type pneumococci and pneumococci deficient in pneumolysin caused ciliary slowing, but penicillin lysis of wild-type, not pneumolysin-deficient, pneumococci increased the extent of ciliary inhibition. This effect was abolished by antipneumolysin antibody. Ependymal ciliary stasis by purified pneumolysin was also blocked by the addition of antipneumolysin monoclonal antibodies. These data show that antibiotic lysis of Streptococcus pneumoniae can be detrimental to the ciliated ependyma and that antipneumolysin antibody may have a therapeutic potential.

Animals↗

Bordetella bronchiseptica adherence to cilia is mediated by multiple adhesin factors and blocked by surfactant protein A.

In the virulent state (Bvg+), Bordetella bronchiseptica expresses adhesins and toxins that mediate adherence to the upper airway epithelium, an essential early step in pathogenesis. In this study, we used a rabbit tracheal epithelial cell binding assay to test how specific host or pathogen factors contribute to ciliary binding. The host antimicrobial agent surfactant protein A (SP-A) effectively reduced ciliary binding by Bvg+ B. bronchiseptica. To evaluate the relative contributions of bacterial adhesins and toxins to ciliary binding, we used mutant strains of B. bronchiseptica in the binding assay. When compared to Bvg+ or Bvg- phase-locked B. bronchiseptica strains, single-knockout strains lacking one of the known adhesins (filamentous hemagglutinin, pertactin, or fimbriae) displayed an intermediate ciliary binding capacity throughout the coincubation. A B. bronchiseptica strain deficient in adenylate cyclase-hemolysin toxin also displayed an intermediate level of adherence between Bvg+ and Bvg- strains and had the lowest ciliary affinity of any of the Bvg+ phase strains tested. A B. bronchiseptica strain that was missing dermonecrotic toxin also displayed intermediate binding; however, this strain displayed ciliary binding significantly higher than most of the adhesin knockouts tested. Taken together, these findings suggest that virulent-state B. bronchiseptica expresses multiple adhesins with overlapping contributions to ciliary adhesion and that host production of SP-A can provide innate immunity by blocking bacterial adherence to the ciliated epithelium.

Adhesins, Bacterial↗

Neonatal cilia: ultrastructure.

The number of inner and outer dynein arms and gross cilial abnormalities of well newborn children and adults were similar. Inability to see all nine outer dynein arms in healthy adults may be due to technique and not recent infection or congenital cilial malformation.

Adult↗

Ectopic cilia.

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Adolescent↗

Abnormal cilia.

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Cilia↗

Abnormal cilia.

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Cilia↗

Orientation of respiratory tract cilia in patients with primary ciliary dyskinesia, bronchiectasis, and in normal subjects.

A reproducible technique, utilising a graphics tablet and a personal computer for measuring ciliary orientation from electron micrographs of ciliated epithelium, was assessed. Ciliary deviation was measured in 47 normal subjects (mean ciliary deviation +/- 1 SD was 14.6 (3.3 degrees)), in eight patients with bronchiectasis and normal ciliary function (15.1 (6.5 degrees], and in seven patients with primary ciliary dyskinesia (38.7 (7.8 degrees); significantly greater than the first two groups). Measurements of ciliary deviation at the tip, base, and basal feet showed very little variation along the ciliary shaft in all three groups, suggesting that valid measurements of ciliary deviation can be made at any level of the cilium. Mean ciliary deviation in normal subjects was always less than 30 degrees; all patients with a mean ciliary deviation of greater than 30 degrees had recurrent respiratory tract disease. Four of seven patients with primary ciliary dyskinesia had ciliary disorientation; in one this was the only defect. Measurements of inter- and intraobserver variability using this method showed a maximum difference between observations of 4.1 degrees. It is suggested that ciliary orientation should be measured in patients suspected of having defective ciliary function or structure, or both.

Adolescent↗

Usher syndrome type I associated with bronchiectasis and immotile nasal cilia in two brothers.

Usher syndrome type I is an autosomal recessive disease characterised by congenital sensorineural deafness, involvement of the vestibular system, and progressive visual loss owing to retinitis pigmentosa. Here we report the association of this disease with bronchiectasis, chronic sinusitis, and reduced nasal mucociliary clearance in two sibs and we suggest Usher syndrome type I could be a primary ciliary disorder.

Abnormalities, Multiple↗

Immotile cilia.

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Adult↗

Ion channel classes in purified olfactory cilia membranes: planar lipid bilayer studies.

Ciliary membrane fragment fusion to planar lipid bilayers resulted in the insertion of four ion channel types. cAMP-activated, cation-selective channels could be detected only in the absence of Ca2+ and had a conductance of 23 pS. They exhibited an apparent dissociation constant (Kd) for the cyclic nucleotide of approximately 30 microM and an estimated permeability ratio (PNa/PK) of 2.4. The cAMP cation-selective channel coinserted with a K(+)-selective channel refractory to cAMP, Ca2+, and D-myo-inositol 1,4,5-trisphosphate. This K+ channel was voltage independent and exhibited open-conductance substates of 60 and 112 pS. cAMP was also found to modulate a novel K+ channel with a Kd = 140 microM. It displayed three nearly equally spaced open substates with conductances of 34, 80, and 130 pS. In the absence and in the presence of cAMP the probability of occurrence of the open substates was binomially distributed. A fourth channel type was a Ca(2+)-activated K+ channel with a conductance of 240 pS. It was blocked by charybdotoxin at nanomolar concentrations (Kd = 3 nM). These results add support to the idea that, besides cAMP-activated cation-selective channels, vertebrate chemosensory olfactory membranes possess an arrangement of ion channels.

Animals↗

Interneuronal projections to identified cilia-activating pedal neurons in Hermissenda.

Neural networks have been shown to support the generation of more than one behavioral motor act. In the nudibranch mollusk Hermissenda, Pavlovian conditioning results in light, the conditioned stimulus (CS), evoking both inhibition of locomotion and foot contraction. The synaptic organization of the eyes and optic ganglion is well documented; however, the characterization of the neural network mediating visually modulated behaviors is incomplete. We have now characterized synaptic connections between identified photoreceptors and a newly identified interneuron (II(b)), identified synaptic projections from type I and type II interneurons to an inhibitory interneuron (III(i)) and to two newly identified pedal neurons, VP1 and VP2. Here we show that VP1 activates ciliary movement on the anterior foot and VP2 innervates the anterior foot and ventral tentacle. Stimulation of the photoreceptors with light produced two effects on the activity of VP1 and VP2. First, light inhibits type I(i) and II(i) interneurons and disinhibits VP1 and VP2. Depolarization of type II(e) interneurons also disinhibits VP1 and VP2. Second, the light-elicited depolarization and increased tonic activity of VP1 and VP2 is produced by excitatory synaptic input from ipsilateral and contralateral type II(b) interneurons. Pedal neurons VP1 and VP2 receive similar synaptic input from type I, II, and III(i) interneurons; this is in agreement with previous research showing that the visual pathway influences both ciliary locomotion and foot movement. The organization of the visual system in Hermissenda provides for the expression of cellular and synaptic plasticity supporting learning without altering the networks ability to carry out the requirements for normal visual processing.

Animals↗