Effect of Leukotriene D4 on Ciliary Activity in Human, Guinea-Pig and Rat Respiratory Mucosa

Joki, Susanna; Saano, Veijo; Koskela, Tommi; Toskala, Elina; Bray, M.A.; Nuutinen, Juhani

doi:10.1006/pulp.1996.0029

Cited by 14 publications

(8 citation statements)

References 6 publications

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“…Indeed, there is a suggestion that inflammatory mediators such as leukotriene D 4 may impair ciliary orientation. 39 In addition, studies done on quail oviduct and Xenopus larval skin suggest that ciliary polarity and orientation are influenced by the normal development of the apical cytoskeleton and normal tissue patterning. 40,41 Thus, recent evidence of aberrant epithelial repair seen in asthmatic epithelium 6,7 could also provide a plausible mechanism contributing to ciliary disorientation seen in asthma.…”

Section: Discussionmentioning

confidence: 99%

Ciliary dysfunction and ultrastructural abnormalities are features of severe asthma

Thomas¹,

Rutman²,

Hirst³

et al. 2010

Journal of Allergy and Clinical Immunology

167

122

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Section: Discussionmentioning

confidence: 99%

Ciliary dysfunction and ultrastructural abnormalities are features of severe asthma

Thomas¹,

Rutman²,

Hirst³

et al. 2010

Journal of Allergy and Clinical Immunology

167

122

View full text Add to dashboard Cite

“…Related to these abnormalities in function, subjects with severe asthma have more ciliary disorientation, ciliary depletion, and microtubular defects compared to both normal controls and subjects with mild asthma (144). Sputum from asthma patients has an inhibitory effect on cilia beating in bronchial epithelial explants (145) A number of mediators implicated in asthma, including prostaglandins, bradykinin, prostacyclin and leukotriene D4 increase cilia beat frequency (56, 146), while varying effects on ciliary beat frequency have been reported for histamine and leukotriene C4 (56, 146, 147). …”

Section: Acquired Disorders Of Airway Ciliamentioning

confidence: 99%

Cilia Dysfunction in Lung Disease

Tilley

Walters²,

Shaykhiev³

et al. 2015

Annu. Rev. Physiol.

344

308

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A characteristic feature of the human airway epithelium is the presence of ciliated cells bearing motile cilia, specialized cell surface projections containing axonemes comprised of microtubules and dynein arms, which provide ATP-driven motility. In the airways, cilia function in concert with airway mucus to mediate the critical function of mucociliary clearance, cleansing the airways of inhaled particles and pathogens. The prototypical disorder of respiratory cilia is primary ciliary dyskinesia, an inherited disorder that leads to impaired mucociliary clearance, repeated chest infections, and progressive destruction of lung architecture. Numerous acquired lung diseases are also marked by abnormalities in both cilia structure and function. In this review we summarize current knowledge regarding airway ciliated cells and cilia, how they function to maintain a healthy epithelium, and how disorders of cilia structure and function contribute to inherited and acquired lung disease.

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“…Leukotrienes C 4 and D 4 as lipid mediators (products of arachidonic acid degradation by 5-lipooxygenase) increase the ciliary beat frequency in human upper airway mucosa in vitro (Cyrus et al, 1998). Moreover, experimental findings suggest that LTD 4 exerts cilio-excitatory effects in human, guinea pig, and rat respiratory mucosa with impaired cilia orientation and mucus production (Joki et al, 1996).…”

Section: Antileukotriensmentioning

confidence: 99%

Respiratory Cilia as a Therapeutic Target of Phosphodiesterase Inhibitors

2020

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Mucociliary clearance is an essential airway defense mechanism dependent predominantly on the proper ciliary function and mucus rheology. The crucial role of cilia is evident in`a variety of respiratory diseases, as the ciliary dysfunction is associated with a progressive decline in lung function over time. The activity of cilia is under supervision of multiple physiological regulators, including second messengers. Their role is to enable a movement in coordinated metachronal waves at certain beat frequency. Ciliary function can be modulated by various stimuli, including agents from the group of beta 2 agonists, cholinergic drugs, and adenosine triphosphate (ATP). They trigger cilia to move faster in response to elevated cytoplasmic Ca 2+ originated from intracellular sources or replenished from extracellular space. Well-known cilia-stimulatory effect of Ca 2+ ions can be abolished or even reversed by modulating the phosphodiesterase (PDE)-mediated breakdown of cyclic adenosine monophosphate (cAMP) since the overall change in ciliary beating has been dependent on the balance between Ca 2+ ions and cAMP. Moreover, in chronic respiratory diseases, high ATP levels may contribute to cAMP hydrolysis and thus to a decrease in the ciliary beat frequency (CBF). The role of PDE inhibitors in airway cilia-driven transport may help in prevention of progressive loss of pulmonary function often observed despite current therapy. Furthermore, administration of selective PDE inhibitors by inhalation lowers the risk of their systemic effects. Based on this review we may conclude that selective (PDE1, PDE4) or dual PDE inhibitors (PDE3/4) increase the intracellular level of cyclic nucleotides in airway epithelial cells and thus may be an important target in the development of new inhaled mucokinetic agents. Further research is required to provide evidence of their effectiveness and feasibility regarding their cilia-modulating properties.

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Effect of Leukotriene D4 on Ciliary Activity in Human, Guinea-Pig and Rat Respiratory Mucosa

Cited by 14 publications

References 6 publications

Ciliary dysfunction and ultrastructural abnormalities are features of severe asthma

Ciliary dysfunction and ultrastructural abnormalities are features of severe asthma

Cilia Dysfunction in Lung Disease

Respiratory Cilia as a Therapeutic Target of Phosphodiesterase Inhibitors

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