Inhaled leukotrienes cause bronchoconstriction and neutrophil accumulation in horses

Marr, K.A.; Lees, P.; Page, Clive; Cunningham, Fiona

doi:10.1016/s0034-5288(98)90129-1

Cited by 22 publications

(21 citation statements)

References 22 publications

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“…Results of previous studies [7][8][9]14 indicate that LTD 4 causes bronchoconstriction of the equine airways in vitro and in vivo. In our study, we evaluated the therapeutic benefit of the LTD 4 -receptor antagonist L-708,738 for the treatment of heaves.…”

Section: Discussionmentioning

confidence: 93%

“…Results indicate that LTD 4 contracts isolated equine parenchymal smooth muscle 7 and enhances contraction of small airways after electric field stimulation. 8 The findings that inhalation of LTD 4 by horses with heaves induces bronchoconstriction 9 and that the concentration of LTC 4 in bronchoalveolar lavage fluid (BAL) of horses with coughing and exercise intolerance a is high further supports a possible role of cysteinyl LT in respiratory diseases of horses.…”

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confidence: 96%

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Comparison of effects of dexamethasone and the leukotriene D4 receptor antagonist L-708,738 on lung function and airway cytologic findings in horses with recurrent airway obstruction

Lavoie¹,

Léguillette²,

Pasloske³

et al. 2002

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L-708,738 was bioavailable after oral administration and sustained concentrations in plasma during the dosing period that exceeded in vitro efficacy values. However, airway function did not improve, suggesting that either drug concentrations in the lungs were subtherapeutic or that cysteinyl LT may not be important mediators of airway inflammation in heaves. Results provide the first evidence of cysteinyl LT1 receptors in airways of horses.

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Section: Discussionmentioning

confidence: 93%

mentioning

confidence: 96%

Comparison of effects of dexamethasone and the leukotriene D4 receptor antagonist L-708,738 on lung function and airway cytologic findings in horses with recurrent airway obstruction

Lavoie¹,

Léguillette²,

Pasloske³

et al. 2002

ajvr

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“…One study showed that inhaled LTB 4 in horses causes neutrophil recruitment. 18 Authors of another study concluded that increased concentrations of LTB 4 in airways of RAO-affected horses contributes to neutrophil infiltration and the ongoing inflammation associated with RAO. 16 In humans, histamine stimulation of bronchial epithelial cells involves binding at H1 receptors, production of LTB 4 , activation of the transcription factor NF-kB, and increased expression of IL-8.…”

Section: Discussionmentioning

confidence: 99%

Rapid, Multiwell Colorimetric Assay for Measuring Neutrophil Chemoattractant Activity in Bronchoalveolar Lavage Fluid of Horses with Recurrent Airway Obstruction

et al. 2006

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Abstract. The criteria used to diagnose recurrent airway obstruction (RAO) in affected horses include demonstration of reversible lower airway obstruction and greater than 25% neutrophils in bronchoalveolar lavage fluid (BALF). Additional objective laboratory tests are needed to improve diagnostic accuracy and to monitor response to treatment. The goal of this study was to determine if neutrophil chemoattractant activity of BALF could be measured by using a previously described, rapid, multiwell colorimetric assay for chemotaxis. In this assay, neutrophils that have migrated through a membrane filter are collected into the bottom well of a disposable chemotaxis-cell migration chamber. The number of viable cells collected in the bottom well is quantified by measurement of the reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenol tetrazolium bromide (MTT), which is reduced by dehydrogenase in mitochondria of live cells. The number of migrating cells corresponds to the amount of MTT reduced, which is measured with an enzyme-linked immunosorbent assay plate reader. Fourteen adult horses were enrolled in this study, 7 of which had owner histories consistent with RAO. Each horse was sedated, a bronchoalveolar lavage tube was passed, and saline was infused and immediately aspirated. An aliquot of BALF was used for differential cell count, and BALF supernatant was harvested to assess neutrophil chemoattractant activity. Normal control horses and RAOaffected horses were distinguished according to clinical signs and percent neutrophils in BALF. Neutrophil chemoattractant activity of BALF was significantly greater in RAO-affected horses (P 5 0.001) compared with control horses. This assay may be useful in future studies for monitoring response to therapy in RAOaffected horses.

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“…In horses, aerosol administration of LTB 4 is followed by migration of neutrophils into the lung. 9 In humans, LTB 4 stimulates cytokine production and activates the transcription factor, nuclear factor-κ κB (NF-κ κB), thereby promoting transcription of inflammatory genes and cytokine production. 10 High levels of NF-κB activity develop in bronchial cells during acute airway obstruction in RAO-affected horses.…”

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confidence: 99%

Assessment of leukotriene B4 production in leukocytes from horses with recurrent airway obstruction

Lindberg

Robinson²,

Näsman-Glaser³

et al. 2004

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Inhaled leukotrienes cause bronchoconstriction and neutrophil accumulation in horses

Cited by 22 publications

References 22 publications

Comparison of effects of dexamethasone and the leukotriene D4 receptor antagonist L-708,738 on lung function and airway cytologic findings in horses with recurrent airway obstruction

Comparison of effects of dexamethasone and the leukotriene D4 receptor antagonist L-708,738 on lung function and airway cytologic findings in horses with recurrent airway obstruction

Rapid, Multiwell Colorimetric Assay for Measuring Neutrophil Chemoattractant Activity in Bronchoalveolar Lavage Fluid of Horses with Recurrent Airway Obstruction

Assessment of leukotriene B4 production in leukocytes from horses with recurrent airway obstruction

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