Mechanisms of action of Pseudomonas aeruginosa pyocyanin on human ciliary beat in vitro

Kanthakumar, K.; Taylor, Graham W.; Tsang, K. T.; Cundell, Diana R.; Rutman, A; Smith, Susan; Jeffery, P. K.; Cole, Peter; Wilson, Robert

doi:10.1128/iai.61.7.2848-2853.1993

Cited by 94 publications

(58 citation statements)

References 38 publications

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“…Pyocyanin (20 tyg ml-l) was used in all experiments. This concentration has been observed in the sputum of infected patients , and in previous experiments in our laboratory (Kanthakumar et al, 1993) caused CBF to fall to about half of control by 4 h, disruption of epithelium integrity at 3 h, and marked falls in both intracellular cyclic AMP and ATP. For each experiment the sample of nasal epithelial strips in medium 199 was divided into four equal aliquots.…”

Section: Effect Of Salmeterol On Pyocyanin-induced Ciliary Slowingsupporting

confidence: 77%

“…The sample of epithelium was divided, and sealed microscope coverslip-slide preparations were constructed for assessment by light microscopy. CBF was measured photometrically from ten identified sites on at least six strips of epithelium at 370C as previously described (Wilson et al, 1987;1988;Kanthakumar et al, 1993). Ciliary dyskinesia (loss of the normal coordinated pattern of ciliary beating), ciliostasis (absence of ciliary beating), and disruption of the integrity of the epithelial surface (irregularity and break-up of the previously smooth intact surface) were recorded when present.…”

Section: Methodsmentioning

confidence: 99%

“…Levels of ATP in nasal epithelium were measured spectrophotometrically (Sigma, UK). Cyclic AMP levels were measured by enzyme immunoassay (Amersham, UK) (Kanthakumar et al, 1993). Nasal epithelial samples (n = 6) were treated with pyocyanin (20 ytg ml-') for 2 h in the presence or absence of salmeterol (2 x 10-7 M).…”

Section: Atp and Cyclic Amp Measurementmentioning

confidence: 99%

“…We have recently shown that pyocyanin-induced slowing of human ciliary beat in vitro is associated with a fall in intracellular adenosine 3':5'-cyclic monophosphate (cyclic AMP) and adenosine 5'-triphosphate (ATP). Ciliary beat slowing could be prevented by treating the epithelial cells with agents known to increase cyclic AMP levels (Kanthakumar et al, 1993).…”

Section: Introductionmentioning

confidence: 99%

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Effect of salmeterol on human nasal epithelial cell ciliary beating: inhibition of the ciliotoxin, pyocyanin

Kanthakumar

Cundell

Johnson

et al. 1994

British J Pharmacology

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Patients with airway infection by Pseudomonas aeruginosa have impaired mucociliary clearance. Pyocyanin is a phenazine pigment produced by P. aeruginosa which is present in the sputum of colonized patients, slows human ciliary beat frequency (CBF) in vitro and slows mucociliary transport in vivo in the guinea‐pig. We have investigated the effect of salmeterol, a long‐acting β2‐adrenoceptor agonist, on pyocyanin‐induced slowing of human CBF in vitro. Salmeterol (2 × 10−7 m) was found to reduce pyocycanin (20 μg ml−1)‐induced slowing of CBF by 53% and the fall in intracellular adenosine 3′:5′‐cyclic monophosphate (cyclic AMP) by 26% and ATP by 29%. Another β2‐adrenoceptor agonist, isoprenaline (2 × 10−7 m), also inhibited pyocyanin‐induced slowing of CBF by 39%. The effects of salmeterol (30 min preincubation) persisted after washing the cells. Propranolol (10−7 m) and the β2‐specific antagonist, ICI 118551 (10−6 m) blocked the protective effects of salmeterol completely, but atenolol (10−6 m) was less effective. These results suggested that the effects of salmeterol on pyocyanin‐induced effects were mediated primarily via the stimulation of β2‐adrenoceptors. Pyocyanin‐induced ciliary slowing is associated with a substantial fall in intracellular cyclic AMP and ATP. Salmeterol reversed the effects of pyocyanin on cyclic AMP and ATP. Mucociliary clearance is an important defence mechanism of the airways against bacterial infection. Salmeterol may benefit patients colonized by P. aeruginosa, not only by its bronchodilator action, but also by protecting epithelial cells from pyocyanin‐induced slowing of CBF.

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Section: Effect Of Salmeterol On Pyocyanin-induced Ciliary Slowingsupporting

confidence: 77%

Section: Methodsmentioning

confidence: 99%

Section: Atp and Cyclic Amp Measurementmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Effect of salmeterol on human nasal epithelial cell ciliary beating: inhibition of the ciliotoxin, pyocyanin

Kanthakumar

Cundell

Johnson

et al. 1994

British J Pharmacology

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“…Low levels of B cells were not associated with low immunoglobulin levels. Six of the subjects had a CD4 count below 300 cells/µl and appeared to have idiopathic CD4 lymphocytopaenia, which is associated with opportunistic infections [24].…”

Section: Discussionmentioning

confidence: 99%

Assessing immune function in adult bronchiectasis

King

Hutchinson

Holmes

et al. 2006

Clinical and Experimental Immunology

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SummaryBronchiectasis is characterized by chronic airway infection and damage and remains an important health problem. Recent literature has emphasized the role of host defence and immune deficiency in the pathogenesis of bronchiectasis, but there have been few studies of immune function in adult bronchiectasis. A comprehensive screen of immune function was conducted in 103 adult patients with bronchiectasis, encompassing full blood examinations, immunoglobulins and IgG isotypes, complement levels, lymphocyte subsets and neutrophil function. Full blood examinations were normal in this cohort, as were complement levels. Statistical analysis confirmed that a significant number of subjects had low levels of IgG3 (13 patients), B cell lymphocytes (six patients) and T helper cell lymphocytes (seven patients) when compared with controls ( P < < < < 0·05). The most common abnormality was found with testing of the neutrophil oxidative burst. All subjects had a normal neutrophil phagocytic function but 33 of the subjects had an oxidative burst that was below the normal range ( P < < < < 0001). Almost half the group (45 subjects) had abnormally low levels of one of these four parameters. The findings of low B cells, Th cells and oxidative burst in bronchiectasis are novel. The results emphasize the importance of immune function assessment for adult bronchiectasis.

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Bronchiectasis

Seaton¹

2000

Crofton and Douglas's Respiratory Diseases

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Mechanisms of action of Pseudomonas aeruginosa pyocyanin on human ciliary beat in vitro

Cited by 94 publications

References 38 publications

Effect of salmeterol on human nasal epithelial cell ciliary beating: inhibition of the ciliotoxin, pyocyanin

Effect of salmeterol on human nasal epithelial cell ciliary beating: inhibition of the ciliotoxin, pyocyanin

Assessing immune function in adult bronchiectasis

Bronchiectasis

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