The effects of salmeterol and salbutamol on ciliary beat frequency of cultured human bronchial epithelial cells, in vitro

Devalia, JL; Sapsford, RJ; Rusznák, C.; Toumbis, Michael; Davies, R. Jeremy H.

doi:10.1016/0952-0600(92)90068-r

Cited by 115 publications

(76 citation statements)

References 16 publications

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“…The long-acting β 2 -agonist salmeterol raises the level of cAMP in epithelial cells [48], and partially inhibits the action of pyocyanin in vitro [49]. Therefore, salmeterol may benefit patients colonized by P. aeruginosa not only by its bronchodilating action but also by protecting cilia from the cAMPdependent effects of pyocyanin.…”

Section: Bacterial Interactions With Ciliamentioning

confidence: 99%

The biology of bacterial colonization and invasion of the respiratory mucosa

Wilson

Dowling²,

Jackson³

1996

European Respiratory Journal

136

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Despite being regularly exposed to particulate matter during breathing, which contains bacteria from the commensal flora in the nasopharynx and from the environment, the healthy lung is kept sterile by efficient defence mechanisms. Bacterial infections of the respiratory mucosa represent a dynamic interaction, to which both host and bacterial factors contribute.The abnormal host defences associated with chronic respiratory infections (e.g. cystic fibrosis and other forms of bronchiectasis) serve to emphasize their permissive role. The bacteria that cause bronchial infections possess a wide array of potential virulence factors that contribute to their pathogenicity. Many of these factors influence the mucociliary system, an important first-line defence mechanism. The multiplication, spread and persistence of bacteria within the bronchial lumen, and consequent damage to the epithelium, stimulates a chronic inflammatory response, which also impairs mucociliary clearance and damages lung tissue.A greater understanding of host-bacterial interactions during mucosal infections should in the future lead to the development of new therapies and treatment strategies.

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Section: Bacterial Interactions With Ciliamentioning

confidence: 99%

The biology of bacterial colonization and invasion of the respiratory mucosa

Wilson

Dowling²,

Jackson³

1996

European Respiratory Journal

136

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“…The cells were suspended in approximately 5 mL of Medium 199 (Sigma, Australia) to maintain cell viability and aliquots of cell suspensions were treated with the drugs for 15-30 min. The range of concentrations of SS and MA tested ranged from 10 −8 to 10 −3 M. Based on the results of ciliary beat frequency (CBF) stimulation from individual drug and previous study by Devalia et al (18), indicated that the optimal concentrations to achieve significant increase in CBF were between 10 −6 and 10 −4 M on cultured bronchial epithelial cells. Consequently, in this study, the concentrations of SS used were 0.5×10 −6 M and 1×10 −6 M together with 10 −3 M of MA based on the combination therapy formulated.…”

Section: Ciliary Activitymentioning

confidence: 99%

Combined Inhaled Salbutamol and Mannitol Therapy for Mucus Hyper-secretion in Pulmonary Diseases

Ong

Traini

Ballerin

et al. 2014

AAPS J

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Abstract. This study focuses on the co-engineering of salbutamol sulphate (SS), a common bronchodilator, and mannitol (MA), a mucolytic, as a potential combination therapy for mucus hypersecretion. This combination was chosen to have a synergic effect on the airways: the SS will act on the β 2 -receptor for relaxation of smooth muscle and enhancement of ciliary beat frequency, whilst mannitol will improve the fluidity of mucus, consequently enhancing its clearance from the lung. A series of co-spray-dried samples, containing therapeutically relevant doses of SS and MA, were prepared. The physico-chemical characteristics of the formulations were evaluated in terms of size distribution, morphology, thermal and moisture response and aerosol performance. Additionally, the formulations were evaluated for their effects on cell viability and transport across air interface Calu-3 bronchial epithelial cells, contractibility effects on bronchial smooth muscle cells and cilia beat activity using ciliated nasal epithelial cells in vitro. The formulations demonstrated size distributions and aerosol performance suitable for inhalation therapy. Transport studies revealed that the MA component of the formulation enhanced penetration of SS across the complex mucus layer and the lung epithelia cells. Furthermore, the formulation in the ratios of SS 10 −6 and MA 10 −3 M gave a significant increase in cilia beat frequency whilst simultaneously preventing smooth muscle contraction associated with mannitol administration. These studies have established that co-spray dried combination formulations of MA and SS can be successfully prepared with limited toxicity, good aerosol performance and the ability to increase ciliary beat frequency for improving the mucociliary clearance in patients suffering from hyper-secretory diseases, whilst simultaneously acting on the underlying smooth muscle.

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“…For example, fibroblast activation has been observed (Schneider et al, 2010). ALI cultures are also useful to analyze ciliary beat frequency in response to various stimuli (Bayram et al, 1998;Devalia et al, 1992).…”

Section: Co-culture and Pathophysiological Modelsmentioning

confidence: 99%

Non-animal models of epithelial barriers (skin, intestine and lung) in research, industrial applications and regulatory toxicology

Gordon

Daneshian

Bouwstra

et al. 2015

ALTEX

124

103

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SummaryModels of the outer epithelia of the human body -namely the skin, the intestine and the lung -have found valid applications in both research and industrial settings as attractive alternatives to animal testing. A variety of approaches to model these barriers are currently employed in such fields, ranging from the utilization of ex vivo tissue to reconstructed in vitro models, and further to chip-based technologies, synthetic membrane systems and, of increasing current interest, in silico modeling approaches. An international group of experts in the field of epithelial barriers was convened from academia, industry and regulatory bodies to present both the current state of the art of non-animal models of the skin, intestinal and pulmonary barriers in their various fields of application, and to discuss research-based, industry-driven and regulatory-relevant future directions for both the development of new models and the refinement of existing test methods. Issues of model relevance and preference, validation and standardization, acceptance, and the need for simplicity versus complexity were focal themes of the discussions. The outcomes of workshop presentations and discussions, in relation to both current status and future directions in the utilization and development of epithelial barrier models, are presented by the attending experts in the current report.

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The effects of salmeterol and salbutamol on ciliary beat frequency of cultured human bronchial epithelial cells, in vitro

Cited by 115 publications

References 16 publications

The biology of bacterial colonization and invasion of the respiratory mucosa

The biology of bacterial colonization and invasion of the respiratory mucosa

Combined Inhaled Salbutamol and Mannitol Therapy for Mucus Hyper-secretion in Pulmonary Diseases

Non-animal models of epithelial barriers (skin, intestine and lung) in research, industrial applications and regulatory toxicology

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