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KPL1, which encodes a novel PH domain-containing protein, is induced during ciliated cell differentiation of rat tracheal epithelial cells.

Using differential display, we have identified a novel gene, KPL1, induced in rat tracheal epithelial (RTE) cells grown under conditions which stimulate ciliogenesis. The KPL1 protein is predicted to contain a pleckstrin homology (PH) domain, which has been found in numerous signal transduction and cytoskeletal proteins. These domains are thought to function by recruiting proteins to cellular membranes, and they have been shown to bind phosphoinositols and the beta/gamma subunit of G proteins. We have cloned rat and human KPL1; the predicted protein translations are 94% identical. Alternate transcripts exist in rat and human tracheal cells that predict a protein which contains a 35-amino acid insert. KPL1 was upregulated in RTE cultures undergoing mucociliary but not squamous differentiation; and in cultures undergoing mucociliary differentiation, KPL1 expression most closely paralleled that of a marker of ciliated cell differentiation (axonemal dynein heavy chain) and not a marker of mucous cell differentiation (mucin 5AC). As a new member of the family of PH domain-containing proteins, KPL1 may have a unique role in ciliated cell differentiation or function.

Amino Acid Sequence↗

Intracellular recording of potential oscillations in ciliated cells exposed to ionizing radiation.

Intracellular potential oscillations of the ciliated cells of the rabbit's trachea have been measured by means of glass capillary microelectrodes during exposure of the cells to ionizing radiation. The electrophysiologic activity was fairly stable during the entire exposure at a total administered dose of 10.0 Gy. This finding is contradictory to the change in mucociliary activity obtained under the same conditions when measured with a light beam reflex method, but is in agreement with the findings regarding the influence of radiation on the membrane potentials as far as nerves and muscles are concerned.

Action Potentials↗

Membrane progesterone receptor gamma: tissue distribution and expression in ciliated cells in the fallopian tube.

Non-genomic, rapid actions of steroids have long been known, suggesting the possible presence of non-classical steroid receptors. A membrane receptor for progestins (mPR) was recently described in the spotted seatrout, and transcripts of three related receptors (alpha, beta, and gamma) were subsequently identified in other species including human and mouse. To begin exploring the roles of mPRgamma in mammals, we have generated an antibody against this receptor. The specificity of the antibody was demonstrated by both overexpression and RNA interference experiments. Using the antibody, we show that mPRgamma is expressed in female mouse reproductive tissues such as ovary and fallopian tube, and also in the lung and liver of both sexes. Immunohistochemical studies revealed that mPRgamma is associated with the apical membrane of ciliated cells facing the lumen of the fallopian tube. The presence of mPRgamma in ciliated cells of the fallopian tube was also demonstrated in human samples. Rapid effects of progesterone on ciliary beat frequency in the fallopian tube have recently been reported. Together, this suggests a common role for mPRgamma in the regulation of ciliary activity in the fallopian tube and thus gamete transport in mammals. The presence of mPRgamma in lung and liver of mice suggests that the receptor mediates the actions of progesterone outside the reproductive tract as well.

Animals↗

The effects of gossypol on the ultrastructure and function of tracheal ciliated cells.

Gossypol acetic acid inhibits rabbit tracheal ciliary function in a concentration dependent manner. At concentrations of both 10(-4)M and 5 X 10(-5), ciliary beat is reduced to less than 2 beats/sec in approximately 60 min. At 10(-5)M, reduction of frequency is more gradual, requiring 120 min or longer to approach inhibition. The primary site in the cell showing morphological alteration is the mitochondrion, although extended exposure at lower concentrations does seem to cause increase in the amount of endoplasmic reticulum and Golgi. At the time of inhibition of ciliary beat, mitochondria have a washed out matrix, disrupted cristae and extensive infolding of the outer membrane. Some indication of mitochondrial swelling is also evident. Demembranated axonemes exposed to gossypol show the same dose-dependent response as intact ciliated cells. At 10(-4)M gossypol, axonemes are completely inhibited from reactivation. Axonemes can be reactivated in the presence of 10(-5)M gossypol but are quickly inhibited. 10(-6)M gossypol has no inhibitory effect on demembranated axonemes or intact ciliated cells. Gossypol may be acting initially as a direct but reversible inhibitor of axonemal function while damage to mitochondria may be responsible for the long term, non-reversible inhibition of ciliary function.

Animals↗

Fimbrial ciliated cells percentage and epithelial height during and after salpingitis.

Microbiopsies of 191 fimbriae were obtained from 146 patients undergoing laparotomy for acute salpingitis, or tubal surgery after salpingitis. The biopsies were classified in four groups according to the diagnosis at laparotomy: salpingitis, distal occlusion, peritubal adhesions or tuberculosis. The biopsies belonging to the group of distal occlusion were further classified in four sub-groups according to the extent of the lesions observed during the hysterosalpingography and laparoscopy. Since the crucial role of the ciliated epithelium in the ovum transport has been established, the percentage of ciliated cells and the epithelial height were determined in the groups and compared to those observed in fimbriae obtained from fertile women during an ovulatory cycle. Significant differences were noted in all groups when compared to fertile women. Acute salpingitis provoked a rapid and severe deciliation which recovered 3 months after triantibiotherapy. In the groups of distal occlusion, there was a significant correlation between the rate of deciliation and the extent of lesions. This suggests that deciliation of tubal epithelium is a sequela of salpingitis and that the extent of disease allows a prognosis of the percentage of ciliated cells.

Biopsy↗

Stomatin immunoreactivity in ciliated cells of the human airway epithelium.

Stomatin is a widely distributed 32kD membrane protein of unknown function. In biochemical studies it is associated with cholesterol+sphingomyelin-rich 'rafts' in the cytomembrane. Genetic studies in C. elegans, supported by microscopic studies in mammalian tissue and co-expression studies in oocytes, suggest a functional link with the DEG/ENaC (degenerin/epithelial Na+ channel) superfamily of monovalent ion channels. Since ENaC channels play a prominent role in the physiology of the respiratory epithelium, we have studied the immunolocalization of stomatin in mature and developing human airway epithelium by means of Western blot analysis, immunocytochemistry, and immunoelectron microscopy. Stomatin immunoreactivity (stomatin-IR) was found in the ciliated cells of the conductive airway epithelium in a distinct distribution pattern with the strongest signal along the cilia. Immunogold labelling revealed immunogold particles at the basal bodies, along the cilia, and at the membrane of the microvilli. The presence of stomatin-IR paralleled the stages of ciliogenesis in airway development, and its appearance preceded the elongation of the axoneme and the cilial outgrowth. Due to its presence in the different cellular locations in the ciliated cell, we suggest that stomatin is involved in various cellular functions. From its ultrastructural position, stomatin could be a candidate for a membrane-associated mechanotransducer with a role in the control of ciliary motility. Stomatin as a raft protein might be a microtubule associated protein moving along the outer surface of the microtubules to its terminal site of action in the cilia. Stomatin-IR in microvilli supports the hypothesis of a co-localization with beta- and gamma- ENaC and, in conclusion, their potential functional interaction to control the composition of periciliary mucus electrolytes.

Adult↗

Transdifferentiation of ciliated cells during repair of the respiratory epithelium.

Since the lung is repeatedly subjected to injury by pathogens and toxicants, maintenance of pulmonary homeostasis requires rapid repair of its epithelial surfaces. Ciliated bronchiolar epithelial cells, previously considered as terminally differentiated, underwent squamous cell metaplasia within hours after bronchiolar injury with naphthalene. Expression of transcription factors active in morphogenesis and differentiation of the embryonic lung, including beta-catenin, Foxa2, Foxj1, and Sox family members (Sox17 and Sox2), was dynamically regulated during repair and redifferentiation of the bronchiolar epithelium after naphthalene injury. Squamous cells derived from ciliated cells spread beneath injured Clara cells within 6-12 h after injury, maintaining the integrity of the epithelium. Dynamic changes in cell shape and gene expression, indicating cell plasticity, accompanied the transition from squamous to cuboidal to columnar cell types as differentiation-specific cell markers typical of the mature airway were restored. Similar dynamic changes in the expression of these transcription factors occurred in ciliated and Clara cells during regeneration of the lung after unilateral pneumonectomy. Taken together, these findings demonstrate that ciliated epithelial cells spread and transdifferentiate into distinct epithelial cell types to repair the airway epithelium.

Animals↗

Glycolipid receptors for attachment of Mycoplasma hyopneumoniae to porcine respiratory ciliated cells.

Glycolipid receptors for Mycoplasma hyopneumoniae attachment were analyzed by using a thin-layer chromatography (TLC) overlay assay. M. hyopneumoniae bound specifically to sulfatide, globoside, and monosialoganglioside GM3. No binding to sphingomyelin, cerebroside, lactosyl ceramide, ceramide trihexoside, monosialogangliosides GM1 and GM2, disialogangliosides (GD1a, GD1b, and GD3), trisialoganglioside (GT1b), cholesterol, cholesterol sulfate, palmitic acid, tripalmitin, or cholesteryl palmitate was detected. Total lipids extracted from cilia of the swine respiratory epithelium, the natural targets of M. hyopneumoniae infection, were also separated on TLC plates and overlaid with mycoplasmas. M. hyopneumoniae bound specifically to three ciliary glycolipids identified as La, Lb, and Lc. Binding to Lc was stronger than to La and Lb. All three lipids were believed to be sulfated glycolipids, as determined by laminin binding and staining with azure A. Lc was identified as a putative sulfatide because it has a mobility similar to that of authentic sulfatide and comigrated with sulfatide on TLC plates. Laminin bound to La, Lb, and Lc and produced dose-dependent inhibition of adherence of the mycoplasma to the three ciliary receptors. Binding of the mycoplasma to sulfatide, La, Lb, and Lc was partially inhibited by dextran sulfate, heparin, fucoidan, mucin, and chondroitin sulfate B. These substances blocked the adherence of M. hyopneumoniae to cilia and ciliated cells as shown in a previous study (Q. Zhang, T. F. Young, and R. F. Ross, Infect. Immun. 62:1616-1622, 1994). These results indicate that La, Lb, and Lc are the major native receptors for M. hyopneumoniae adherence to ciliated cells.

Animals↗

Ciliated cell remnants in peritoneal dialysis fluid.

Ciliocytophthoria are anucleate remnants of ciliated epithelial cells derived from the lower respiratory tract and female reproductive tract. We report a case of ciliocytophthoria found in the effluent dialysis fluid of a young woman undergoing long-term ambulatory peritoneal dialysis. Inability to identify these "organisms" initially led to an extensive search for parasitic contamination or infection of the peritoneum. After identifying these "organisms" as ciliocytophthoria, a prospective study showed that ciliated cell remnants occur frequently in the effluent dialysate of young women, but not in older women or men. With increasing use of peritoneal dialysis, laboratory personnel can expect to see ciliocytophthoria in peritoneal dialysate effluent and should recognize them as benign, normal findings in young women.

Adult↗

Median raphe cyst of the penis with ciliated cells.

Cystic lesions occurring on the ventral surface of the penis have been classified as median raphe cysts of the penis. They are lined by pseudostratified, columnar or stratified squamous cell epithelium, mimicking the epithelial lining of the male urethra. Ciliated cysts of the human skin are unusual. Cystic lesions containing ciliated cells have been noted to occur in the chest, neck, or head, and bronchogenic origin has been the most accepted explanation for its origin. Other reports show the presence of ciliated cysts on the lower extremities, and the mechanism of formation is still a debated question. A case of median raphe cyst of the penis containing ciliated epithelium is presented. The existing literature about these cutaneous lesions is reviewed, including the possible mechanisms believed to be involved in its origin.

Adult↗

Cyclic changes in ciliation, cell height, and mitotic activity in human tubal epithelium during reproductive life.

The percentage of ciliated cells, the height, and the mitotic index of human oviductal epithelium were studied during the menstrual cycle and under progestogens. A total of 141 fallopian tubes were examined. During the menstrual cycle, a process of ciliation and deciliation was observed. Maximal ciliation was attained around the time of ovulation, particularly in the fimbria where significant differences were noted. Deciliation was observed under progestogen therapy, but this progestogen effect was easily reversible. The decrease of epithelial height observed after ovulation was also found after progestogen therapy. Cyclic mitotic activity was noted during the menstrual cycle. Estrogens influence the mitotic activity of tubal epithelium, whereas endogenous progesterone and progestogens inhibit this estrogenic effect.

Cell Cycle↗

Immunocytochemical localization of tubulin, actin, and myosin in axonemes of ciliated cells from quail oviduct.

Tubulin, actin, and myosin have been localized in isolated demembranated ciliated cells from quail oviduct by immunocytochemistry in both light and electron microscopy by using purified antibodies. The peripheral doublets and the central tubules are stained by the antitubulin whereas the kinetosomes are poorly stained. Actin antibodies clearly stain the axonemes, but only on the proximal-half portion, whereas myosin antibodies stain a small area of the axonemes just above the ciliary neck region.

Actins↗

Effect of 50 kV roentgen rays and cobalt-60 gamma rays on the activity of ciliated cells.

A method capable of continuously recording the changes in the physiologic activity of ciliated cells during irradiation has been used to analyse the importance of photon energy for the early biologic effects of ionizing radiation. Gamma rays from 60Co and 50 kV roentgen rays were used. Important differences were demonstrated and conventional RBE values are not valid for early effects. The results are discussed and RBE for 50 kV roentgen rays has been calculated in respect to early effects of irradiation.

Animals↗

[Pharmacologic studies of cultivated human ciliated cells of the upper respiratory tract].

The ciliary frequency was measured in cultivated ciliated human cells of the upper respiratory tract. An attempt was made to influence this isolated system pharmacologically. Previously, contradictory results have been published regarding the effects of parasympathomimetic and sympathomimetic drugs. We investigated the muscarinic agonist carbachol and the beta 2-adrenoreceptor stimulating drug clenbuterol. Carbachol (10(-3) M) did not modify the ciliary frequency in 6 experiments neither at 37 degrees C nor at 24 degrees C, where the basal frequency was reduced. Spiropent (10(-5) M), a pharmaceutical preparation of clenbuterol and lactose, increased the ciliary frequency in 3 experiments. Clenbuterol, tested in the same concentration in 1 experiment, also caused an increase. Lactose was without effect. The secretolytic drug ambroxol did not influence the ciliary frequency. The neuropeptide substance P which causes an increase in ciliary frequency in the respiratory tract of rabbits in vivo, had no effect on isolated human ciliated cells indicating an indirect effect of this peptide. Calcitonin gene-related peptide which co-exists with substance P in sensory neurons of the airways, increased the ciliary frequency in 1 out of 6 experiments. In conclusion, our results indicate that ciliary activity can be directly modified via beta 2-adrenoreceptors. Other putative neuronal mediators did not reveal clearcut direct activity.

Ambroxol↗

Effect of leukotriene C4 exposure on ciliated cells of the nasal mucosa.

To clarify the effects of leukotriene C4 (LTC4) on human ciliated epithelium, ciliary activity of the ethmoid sinus mucosa was measured photoelectrically in tissue culture. At concentrations ranging from 10(-6)M to 10(-9)M, LTC4 showed minimal effects on the ciliated epithelium during the initial 30 minutes of exposure; thereafter, ciliary inhibition was observed in a concentration- and time-dependent manner. Irrigation of the mucosa with culture medium 15 minutes after exposure prevented the LTC4-induced ciliary inhibition. However, irrigation 60 minutes after exposure failed to inhibit 10(-8)M LTC4-induced ciliary dysfunction and mucosal damage. The LTC4-induced ciliary inhibition was blocked in the presence of FPL-55712 and/or Ly-171883, both leukotriene receptor antagonists. L-serine and sodium tetraborate complex (SBC), a gamma-glutamyl transpeptidase (gamma-GTP) inhibitor, also inhibited the LTC4-induced ciliary inhibition. These findings indicate that LTC4 is converted to LTD4 by gamma-GTP during 60 minutes of exposure, and LTC4 itself has minimal direct effects on the ciliated cells.

Acetophenones↗

Response of ciliated cells during irradiation at different dose rates.

Early radiation effects on the physiologic activity of ciliated cells during exposure have been investigated at 0.34Gy/s and 0.05 Gy/s. The results obtained indicate a more intense early biologic effect at a higher dose rate. The mechanisms of radiation injury are discussed.

Animals↗

An ultrastructural study of primary cilia, abnormal cilia and ciliary knobs from the ciliated cells of the guinea-pig trachea.

Single primary cilia are found in developing as well as mature ciliated cells of guinea-pig tracheal epithelium. A few biciliated cells were observed, and in a rare case one cell had developed four such processes. Primary cilia are characterized by a 9 + 0 microtubular arrangement near the base, while a transition to an 8 + 1 pattern occurs at a slightly more distal position. Spokes are lacking, and dynein arms are absent or incompletely developed. The function, if any, of primary cilia remains unknown. In the population of the motile 9 + 2 cilia atypical forms are very rare, i.e. less than 0.1%. Of the various abnormalities cilia with supernumary microtubules are most common. Only one atypical basal body was observed. Although some of the aberrant forms undoubtedly are non-motile, their very low number suggests that they have no practical influence on the muco-ciliary clearance. Local extrusions of the ciliary membrane, here named ciliary knobs, are believed to be fixation artefacts. It is suggested that they represent circumscribed regions of the ciliary membrane which are sensitive to changes in the environmental osmotic pressure.

Animals↗

[The morphology of ciliated cells in nasal mucosa during a viral infection].

Presentation of the morphological changes in virus-infected nasal ciliated cells was the aim of this report. The most typical abnormalities observed in nasal smears were: intracytoplasmic inclusions, multinucleated cells, absence of cilia, ciliocytophthoria, cytoplasm vacuolization, "naked nuclei" and changes in the cellular shape. Cytological pictures of the alterations connected with viral infection were demonstrated. Presented results were consistent with the observations of other authors. Morphological analysis of the epithelial cells is a very important element of cytological examination of the nasal mucosa.

Adolescent↗