Effects of Oxygen Radicals on Ciliary Motility in Cultured Human Respiratory Epithelial Cells

Yoshitsugu, Masahiko; Matsunaga, Sinya; Hanamure, Yutaka; Rautiainen, Markus; Ueno, Kazuyoshi; Miyanohara, Toshio; Furuta, Shigeru; Fukuda, Katsunori; Ohyama, Masaru

doi:10.1016/s0385-8146(12)80056-3

Cited by 11 publications

(9 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Control cells solely exposed to buffer did not change CBF (0.3 Ϯ 2.1% above baseline; P Ͼ 0.05; n ϭ 7). These results were similar to studies by Yoshitsugu and colleagues (38), who found a transient CBF increase upon X/XO exposure of human maxillary sinus mucosa. In our ALI system, the initial CBF response to X/XO, if present, coincided with a [Ca 2ϩ ] i increase ( Figures 1A and 1F, and Ref.…”

Section: Effect Of X/xo On Cbfsupporting

confidence: 92%

“…Furthermore, most of the reported experiments used brushed cells or tissue culture methods that result in spare cells attached to support surfaces and a lack of HA. One report, however, showed that in cultured cell layers that likely contained HA on their surfaces, exposure to low concentrations of superoxide radicals actually increased CBF (38).…”

Section: Discussionmentioning

confidence: 97%

“…(X/XO) as the source of ROS because previous work had indicated that X/XO was able to stimulate CBF in sinus mucosal tissues that was likely also covered with HA (38).…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Apical Oxidative Hyaluronan Degradation Stimulates Airway Ciliary Beating via RHAMM and RON

Manzanares

Monzón

Savani

et al. 2007

Am J Respir Cell Mol Biol

View full text Add to dashboard Cite

Hyaluronan (HA) is synthesized in high-molecular-weight form at the apical pole of airway epithelial cells, covering the luminal surface. When human airway epithelial cells grown and redifferentiated at the air-liquid interface (ALI) were exposed to xanthine/xanthine oxidase (X/XO), ciliary beat frequency (CBF) increased. This effect was blocked by superoxide dismutase (SOD) and catalase. Inhibition of hyaluronan synthesis inhibited the CBF response to X/XO, while addition of exogenous HA amplified it. A functionally blocking antibody to the receptor for hyaluronic acid-mediated motility (RHAMM) reduced the CBF response to X/XO. Since RHAMM has no transmembrane domain and thus cannot signal on its own, the association of RHAMM with recepteur d'origine nantais (RON), a member of the hepatocyte growth factor receptor family, was explored. Immunohistochemistry of human airway epithelium showed co-localization of RHAMM and RON at the apex of ciliated cells. Physical association of RHAMM and RON was confirmed with co-immunoprecipitations. Macrophage-stimulating protein (MSP), an agonist of RON, stimulated CBF. Genistein, a nonspecific tyrosine kinase inhibitor, and MSP beta chain (beta-MSP), a specific RON inhibitor, blocked the X/XO-induced CBF increase. HA present in the apical secretions of human airway epithelial cells was shown to degrade upon exposure to X/XO, a process inhibited by SOD. Low-molecular-weight HA fragments stimulated CBF, an effect blocked by anti-RHAMM antibody and genistein. These data suggest that high molecular form HA is broken down by reactive oxygen species to form low-molecular-weight fragments that signal via RHAMM and RON to stimulate CBF.

show abstract

Section: Effect Of X/xo On Cbfsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 97%

See 1 more Smart Citation

Apical Oxidative Hyaluronan Degradation Stimulates Airway Ciliary Beating via RHAMM and RON

Manzanares

Monzón

Savani

et al. 2007

Am J Respir Cell Mol Biol

View full text Add to dashboard Cite

show abstract

“…19 Rapid increases in CBF were also induced by "free radicals". 20 Thus our findings suggest a direct effect of oxygen on human respiratory cells.…”

Section: Discussionmentioning

confidence: 51%

Effects of normobaric oxygen on ciliary beat frequency of human respiratory epithelium

Stanek¹,

Brambrink²,

Latorre³

et al. 1998

British Journal of Anaesthesia

View full text Add to dashboard Cite

Respiratory infection is a major cause of morbidity after general anaesthesia. Impairment of respiratory ciliary beat frequency (CBF) by different stress factors causes a decrease in mucus transport rate (MTR). We have tested the effect of different concentrations of oxygen on CBF of human respiratory epithelium in a prospective, randomized, in vitro study. Samples of superficial mucosa of the inferior nasal turbinates of 20 non-smoking healthy volunteers were harvested and exposed to three different oxygen environments (group I = 21% oxygen, group II = 60% oxygen and group III = 95% oxygen) for 2 h. In 50% of the samples, exposure time was prolonged. At 30, 60, 90, 120 and 240 min, light microscopic images of cilia activity were videotaped and CBF was later assessed in slow motion. Compared with baseline, group I showed no difference in CBF throughout the study. CBF was increased in group II from mean 9.7 (SD 0.4) to 11.2 (0.4) Hz (16%, P < 0.001) and in group III from 9.5 (0.6) to 12.1 (0.5) Hz (28%, P < 0.001) at 120 min. After 240 min of exposure to 95% oxygen, the CBF trend in group III was reduced to 11.8 (0.6) Hz but still remained above baseline. We conclude that oxygen appeared to have a dose- and time-dependent accelerating effect on CBF. Prolonged exposure to high oxygen concentrations reversed this trend. Direct oxygen toxicity ("oxygen stress") is a possible explanation for this effect. These changes may result in impaired MTR.

show abstract

“…H 2 O 2 has recently been reported to be increased in the exhaled breath condensate of nonasthmatic subjects with allergic rhinitis (28,41) and has been associated with airway hyperresponsiveness (41). Moreover, ciliary activity, a determining factor in the clearance of secretions in the nose, has been shown to be suppressed by H 2 O 2 (12,35,42). In human respiratory epithelium, H 2 O 2 -mediated ciliary dyskinesia was observed within the first hour, often as early as 15 min after exposure of the cells to H 2 O 2 (12).…”

Section: Discussionmentioning

confidence: 99%

Superoxide dismutase failed to attenuate allergen-induced nasal congestion in ragweed-sensitized dogs

Skorohod

Yeates²

2005

Journal of Applied Physiology

View full text Add to dashboard Cite

We hypothesized that augmentation of antioxidant defenses with exogenous superoxide dismutase (SOD), an enzyme that provides an initial defense against oxidative injury, would attenuate allergen-induced nasal congestion in the canine model of allergic rhinitis. Nasal congestion was evaluated by the measurements of nasal resistance and the volume of the nasal passage. In five nonsensitized dogs, 30,000 U of SOD from bovine erythrocytes delivered by aerosol to the nasal passages before histamine challenge reduced the histamine-induced nasal congestion. At 30 min postchallenge, nasal resistance was 1.14 +/- 0.2 cmH2O.l(-1).min(-1) in the saline pretreatment study vs. 0.36 +/- 0.02 cmH2O.l(-1).min(-1) in the SOD pretreatment study (P < 0.05), and volume of nasal passage was 10.9 +/- 0.5 cm3 vs. 17.4 +/- 1.3 cm3 (P < 0.05), respectively. In five sensitized dogs, however, neither an analogous pretreatment with SOD nor intranasal aerosolized pretreatment with 30,000 U of SOD conjugated to polyethylene glycol attenuated ragweed-induced nasal congestion. Also, systemic application of SOD did not attenuate responses to challenges with histamine and ragweed in nonsensitized and sensitized dogs, respectively. The antioxidant-induced attenuation of nasal congestion in nonsensitized dogs confirms validity of the model and indicates the involvement of free radical-mediated damage in the genesis of the histamine-induced congestion. In sensitized dogs, the data do not support the hypothesis that oxidative stress is a clinically significant component of acute ragweed-induced nasal congestion. The data do not support the use of SOD for acute protection against allergic rhinitis.

show abstract

Effects of Oxygen Radicals on Ciliary Motility in Cultured Human Respiratory Epithelial Cells

Cited by 11 publications

References 28 publications

Apical Oxidative Hyaluronan Degradation Stimulates Airway Ciliary Beating via RHAMM and RON

Apical Oxidative Hyaluronan Degradation Stimulates Airway Ciliary Beating via RHAMM and RON

Effects of normobaric oxygen on ciliary beat frequency of human respiratory epithelium

Superoxide dismutase failed to attenuate allergen-induced nasal congestion in ragweed-sensitized dogs

Contact Info

Product

Resources

About