Synthesis of leukotriene B4, and prostanoids by human alveolar macrophages: analysis by gas chromatography/ mass spectrometry

MacDermot, John; Kelsey, Christopher R.; Waddell, Keith; Richmond, Ramsay; Knight, R.K.; Cole, Peter; Dollery, C. T.; Landon, D. N.; Blair, Ian A.

doi:10.1016/0090-6980(84)90071-6

Cited by 125 publications

(36 citation statements)

References 29 publications

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“…Since PGD 2 production in humans is restricted almost exclusively to the mast cell [25], PGD 2 and its metabolites may be employed as mast cell markers. In some reports macrophages [26] and platelets [27] have been ascribed the ability to synthesize PGD 2 ; however, the levels reported are not of a comparable magnitude to those produced by mast cells.…”

Section: Aamentioning

confidence: 81%

Evidence for mast cell activation during exercise-induced bronchoconstriction

O’Sullivan¹,

Roquet²,

Dahlén³

et al. 1998

Eur Respir J

125

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Exercise-induced bronchoconstriction (EIB) is thought to occur in 70-80% of asthmatics, most commonly amongst those with moderate-to-severe airway hyperresponsiveness [1]. It is characterized by transient airflow obstruction resulting in a Š15% decrease in forced expiratory volume in one second (FEV1) following 5-8 min of exercise. The fall in FEV1 reaches a maximum approximately 10 min after exercise and gradually normalizes over the next hour [2]. The precise pathophysiology of EIB remains unclear, although it is widely accepted that during exercise the upper airways are unable to adequately warm and humidify the increased volumes of inspired air. This results in airway cooling and increased airway fluid osmolality in the lower airways [3,4]. One hypothesis suggests that hyperosmolar triggering of mast cells and possibly other inflammatory cells results in the release of bronchoconstricting mediators, e.g. cysteinyl-leukotrienes (cys-LTs), histamine and prostaglandin (PG)D 2 [5].Previous indications for the participation of mast cell mediators in the pathogenesis of EIB are based on pharmacological data. For example, disodium cromoglycate (DSCG), a drug which stabilizes mast cell membranes, is effective in blunting exercise-induced asthma [6,7]. Pretreatment with a number of H 1 receptor antagonists has been shown to attenuate EIB [8][9][10]; however, the degree of protection afforded by this class of drugs has been modest. More recently, studies employing leukotriene receptor antagonists [11,12] and biosynthesis inhibitors [13] have implicated leukotrienes in the airway bronchoconstrictor response to exercise.The direct approach of measuring mast cell mediator release in response to exercise challenge has yielded ambiguous results. Some studies have reported an elevation in plasma and whole blood histamine concentrations following EIB [14,15], while other studies have failed to verify those findings [16,17]. Apart from the methodological problems encountered when sampling plasma histamine [18] and its short half-life in the circulation, approximately 1 min [19], it has been suggested that elevations in plasma histamine mainly reflect the basophilia which normally accompanies exercise [20]. Increases in the levels of tryptase and PGD 2 , both specific mast cell markers, have been detected in nasal lavage following nasal provocation with cold dry air [21], but not after exercise [22,23].The purpose of this study was to provide evidence to establish mast cell activation as a feature of EIB. To this end, a combination of mast cell markers, 9α,11β-PGF 2 Sullivan, A. Roquet, B. Dahlén, F. Larsen, A. Eklund, M. Kumlin, P.M. O'Byrne, S-E. Dahlén. ©ERS Journals 1998. ABSTRACT: Controversy remains about the causative mediators in the bronchoconstrictive response to exercise in asthma. This study examined whether mast cell activation is a feature of exercise-induced bronchoconstriction by measuring urinary metabolites of mast cell mediators. Evidence for mast cell activation during exercise-induced bronchoconstriction....

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Section: Aamentioning

confidence: 81%

Evidence for mast cell activation during exercise-induced bronchoconstriction

O’Sullivan¹,

Roquet²,

Dahlén³

et al. 1998

Eur Respir J

125

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“…They found LTB4, 5-HETE, and small amounts of A6-trans-LTB4 and A6-trans-1 2-epi-LTB4, but no peptido-LTs. Studying adherent AM, Fels et al (8) demonstrated the release of LTB4 by AM stimulated with A23 187 using HPLC techniques, whereas Damon et al (26) and MacDermot et al (27) identified LTD4 and LTB4, respectively, using mass spectrometry. The synthesis of 5-lipoxygenase and 1 5-lipoxygenase products by blood PMNL has been investigated in detail previously (14,16,28), and the profile of products reported in the present study is in excellent agreement with these reports.…”

Section: Discussionmentioning

confidence: 99%

Decreased leukotriene B4 synthesis in smokers' alveolar macrophages in vitro.

Laviolette¹,

Coulombe²,

Picard³

et al. 1986

J. Clin. Invest.

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Recent studies have shown that alveolar macrophages (AM) are able to release leukotrienes (LTs). Since cigarette smoking inhibits the cyclooxygenase pathway of arachidonic acid metabolism in the AM, we evaluated the LT production by AM from smokers and nonsmokers. AM from nonsmokers, those from smokers showed a 80-90% reduction of 5-HETE and LTB4 synthesis (P < 0.05 to P < 0.001 according to stimulatory conditions). This defective lipoxygenase metabolite production in AM from smokers was observed over a wide range of stimuli concentrations and incubation times; AM from smokers also had lower levels of intracellular (esterified) 5-HETE than nonsmokers' AM. We also studied blood polymorphonuclear leukocytes (PMNL) and no difference in the synthesis of 5-lipoxygenase products in these cells was noticed between smokers and nonsmokers. These data show that cigarette smoking causes a profound inhibition of the 5-lipoxygenase pathway in AM but not in blood PMNL.

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“…PGD 2 is released from mast cells, Th2 cells and dendritic cells [1][2][3][4], it is increased in the airways of patients with asthma [5,6] and there is strong evidence to suggest that it may be involved in the allergic inflammatory response that characterises asthma and allergic rhinitis. In support of this contention are data demonstrating that mice deficient in the DP 1 receptor do not develop an asthmatic phenotype in an ovalbumin-induced asthma model [27].…”

Section: Discussionmentioning

confidence: 99%

“…Prostaglandin D 2 (PGD 2 ) is a major cyclooxygenase product produced by mast cells, with lower levels produced by other cells such as T-helper (Th)2 cells, alveolar macrophages, dendritic cells and platelets [1][2][3][4]. Increased levels of PGD 2 have been found in asthmatics [5,6] and following allergen challenge in patients with asthma [7,8].…”

Section: Introductionmentioning

confidence: 99%

Prostaglandin D₂and the role of the DP₁, DP₂and TP receptors in the control of airway reflex events

et al. 2014

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Prostaglandin D 2 (PGD 2 ) causes cough and levels are increased in asthma suggesting that it may contribute to symptoms. Although the prostaglandin D 2 receptor 2 (DP 2 ) is a target for numerous drug discovery programmes little is known about the actions of PGD 2 on sensory nerves and cough.We used human and guinea pig bioassays, in vivo electrophysiology and a guinea pig conscious cough model to assess the effect of prostaglandin D 2 receptor (DP 1 ), DP 2 and thromboxane receptor antagonism on PGD 2 responses.PGD 2 caused cough in a conscious guinea pig model and an increase in calcium in airway jugular ganglia. Using pharmacology and receptor-deficient mice we showed that the DP 1 receptor mediates sensory nerve activation in mouse, guinea pig and human vagal afferents. In vivo, PGD 2 and a DP 1 receptor agonist, but not a DP 2 receptor agonist, activated single airway C-fibres. Interestingly, activation of DP 2 inhibited sensory nerve firing to capsaicin in vitro and in vivo.The DP 1 receptor could be a therapeutic target for symptoms associated with asthma. Where endogenous PGD 2 levels are elevated, loss of DP 2 receptor-mediated inhibition of sensory nerves may lead to an increase in vagally associated symptoms and the potential for such adverse effects should be investigated in clinical studies with DP 2 antagonists. @ERSpublications Prostaglandin D 2 activates sensory nerves and evokes cough via DP 1 receptors

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Synthesis of leukotriene B4, and prostanoids by human alveolar macrophages: analysis by gas chromatography/ mass spectrometry

Cited by 125 publications

References 29 publications

Evidence for mast cell activation during exercise-induced bronchoconstriction

Evidence for mast cell activation during exercise-induced bronchoconstriction

Decreased leukotriene B4 synthesis in smokers' alveolar macrophages in vitro.

Prostaglandin D₂and the role of the DP₁, DP₂and TP receptors in the control of airway reflex events

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Synthesis of leukotriene B4, and prostanoids by human alveolar macrophages: analysis by gas chromatography/ mass spectrometry

Cited by 125 publications

References 29 publications

Evidence for mast cell activation during exercise-induced bronchoconstriction

Evidence for mast cell activation during exercise-induced bronchoconstriction

Decreased leukotriene B4 synthesis in smokers' alveolar macrophages in vitro.

Prostaglandin D2and the role of the DP1, DP2and TP receptors in the control of airway reflex events

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Product

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Prostaglandin D₂and the role of the DP₁, DP₂and TP receptors in the control of airway reflex events