Leukotrienes C4 and D4 sensitize human neutrophils for hyperreactivity to chemoattractants

Theron, Annette J.; Gravett, Cornelia M; Steel, Helen C.; Tintinger, Gregory Ronald; Feldman, Charles

doi:10.1007/s00011-008-8049-y

Cited by 17 publications

(17 citation statements)

References 23 publications

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“…The individual cell types, activated by various intercellular signal mechanisms, follow specific traffic patterns on various levels in the blood and bronchial tissue (epithelium, mucosal and submucosal layers, smooth muscles and secretory glands), leading to a variety of inflammatory processes, bronchoconstriction, increased sputum production and airway remodeling [2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,47,48,49,50,51,52,53,54,55,56,57,58]. …”

Section: Discussionmentioning

confidence: 99%

“…Patients with allergic bronchial asthma being challenged with an allergen may develop different types of asthmatic response, such as immediate (IAR/EAR) [1,2,3,4,10,14,16,20,23,24,25,32,42], late (LAR) [1,2,3,5,8,10,15,16,19,20,21,22,23,24,25] and recently reported delayed asthmatic response (DYAR) [6,7], probably due to different hypersensitivity mechanisms [1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43]. …”

Section: Introductionmentioning

confidence: 99%

“…Each type of the hypersensitivity mechanism, with its own characteristics and including specific parts, such as particular cell types, individual immunoglobulin classes, specific mediators, chemotactic factors, cytokines, chemokines, CD molecules, adhesion molecules, enzymes, activated cellular and tissue receptors, may lead to a specific clinical manifestation of the lower asthmatic airways [1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43]. …”

Section: Introductionmentioning

confidence: 99%

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Delayed Asthmatic Response to Bronchial Challenge with Allergen-Mediators, Eicosanoids, Eosinophil and Neutrophil Constituents in the Blood and Urine

Pelikán¹

2011

Respiration

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Background: In patients with allergic bronchial asthma, different immunologic mechanisms may participate and lead to different types of asthmatic response to allergen challenge, such as immediate/early (IAR/EAR), late (LAR) or delayed asthmatic response (DYAR). Objectives: In 55 of 397 asthmatics, DYAR has been recorded (p < 0.001) and confirmed by repeated bronchial challenge with the same allergen (p < 0.001). DYAR began between 26 and 32 h, reached a maximum between 32 and 48 h and resolved within 56 h after the challenge. DYAR was associated with various clinical symptoms and diagnostic parameters having diverged from those recorded during the IARs/EARs and LARs. Methods: In 25 of 55 patients, repeated DYAR has been supplemented with the recording of leukotriene B₄ (LTB₄), LTC₄, LTE₄, prostaglandin D₂ (PGD₂), PGE₂, PGF₂_α, thromboxane B₂, lipoxin A₄, eosinophil cationic protein, eosinophil-derived neurotoxin/eosinophil protein X, eosinophilic peroxidase, myeloperoxidase, histamine and tryptase in peripheral blood, and of LTC₄, thromboxane B₂, eosinophil-derived neurotoxin and 9α,11β-PGF₂ in urine, before and up to 72 h after the bronchial allergen challenge, by means of enzyme-linked immunoassay (ELISA/EIA) or ImmunoCAP. Results: DYAR was accompanied by a significant increase in the plasma concentrations of LTB₄ (p < 0.05) and myeloperoxidase (p < 0.05) at 24, 36 and 48 h after the challenge, whereas the plasma/serum or urine concentrations of the other factors did not demonstrate any significant changes (p > 0.05). Conclusions: These results would indicate an active and prominent involvement of neutrophils, in addition to the previously demonstrated role of the Th1 lymphocytes, in the clinical DYAR.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Delayed Asthmatic Response to Bronchial Challenge with Allergen-Mediators, Eicosanoids, Eosinophil and Neutrophil Constituents in the Blood and Urine

Pelikán¹

2011

Respiration

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“…There is, however, evidence that LABAs and montelukast, in addition to their conventional therapeutic activities, possess anti-inflammatory properties [4,[8][9][10]. If operative in vivo, these may complement the anti-inflammatory actions of corticosteroids in controlling severe asthma, especially those types of asthma in which the seemingly corticosteroid-resistant neutrophil [6] is the dominant type of inflammatory cell [11].…”

mentioning

confidence: 99%

Interactive inhibitory effects of formoterol and montelukast on activated human neutrophils

Gravett¹,

Theron²,

Steel³

et al. 2010

Eur Respir J

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The research question addressed in the current study was: do formoterol (1 and 10 nM) and montelukast (2 mM) possess interactive inhibitory effects on activated human neutrophils, particularly in relation to alterations in cyclic AMP and cytosolic Ca 2+ fluxes?Isolated human blood neutrophils were activated with the chemoattractant N-formyl-Lmethionyl-L-leucyl-L-phenylalanine (fMLP) (1 mM) in combination with cytochalasin B (CB; 3 mM). Fura-2-acetoxymethyl ester-based spectrofluorimetry, lucigenin-enhanced chemiluminescence, colorimetric and flow cytometric procedures were used to measure cytosolic Ca 2+ fluxes, production of superoxide, elastase release and beta-2 integrin (CR3) expression, respectively, while cyclic AMP and leukotriene (LT)B 4 were assayed using competitive binding ELISA procedures. Activation of the cells with fMLP/CB resulted in abrupt and sustained increases in cytosolic Ca 2+, as well as release of elastase and production of superoxide and LTB 4 , and expression of CR3, all of which were attenuated by formoterol and montelukast individually, and especially by the combination of these agents. These anti-inflammatory effects of each agent, as well as the combination, were associated with significant increases in cyclic AMP.The findings of the current study may explain the efficacy of montelukast and formoterol when used in combination with inhaled corticosteroids in the treatment of severe asthma, possibly by controlling neutrophil-driven inflammation of the airways.

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“…In fact, neutrophils have been reported to express low levels of LTC 4 and LTD 4 receptors and are slightly responsive to such ligands (30,31). Specific neutrophil ligands were also used including IL-8 and C5a (Fig.…”

Section: Ltb 4 -Mediated Tlr9 Up-regulation In Human Neutrophilsmentioning

confidence: 99%

Leukotriene B4 Potentiates CpG Signaling for Enhanced Cytokine Secretion by Human Leukocytes

Gaudreault

Gosselin

2009

The Journal of Immunology

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TLRs are known to be important in innate host defense against a variety of microbial infections. In particular, TLR9 has been associated with immune defense against different foreign organisms by recognition of unmethylated DNA sequences. In this report, we provide evidence that leukotriene B4 (LTB4) has the capacity to modulate TLR9 expression on human neutrophils. The effect of LTB4 was found to be specific, because related leukotrienes such as LTC4 and LTD4 or neutrophil agonists IL-8 and C5a failed to modulate TLR9 expression in neutrophils. Using fluorochrome-tagged CpG DNA, we observed that LTB4 treatment also increased TLR9 ligand binding in neutrophils. Moreover, LTB4 stimulation potentiates CpG-mediated signaling via an endosome-independent mechanism in human neutrophils, leading to enhanced secretion of proinflammatory cytokines. The increase in cytokine secretion by LTB4 following CpG stimulation of neutrophils was associated with the activation of TGF-β-activated kinase (TAK-1) as well as p38 and c-Jun (JNK) kinases. In contrast, in PBMC LTB4 leads to an increase in cytokine secretion following CpG stimulation but via a MyD88- and endosome-dependent mechanism. As observed in neutrophils, PBMC stimulation with LTB4 in the presence of CpG also results in enhanced TAK-1, p38, and JNK phosphorylation/activation. These data provide new evidence underlying the immunomodulatory properties of LTB4 leading to antimicrobial defense.

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Leukotrienes C4 and D4 sensitize human neutrophils for hyperreactivity to chemoattractants

Cited by 17 publications

References 23 publications

Delayed Asthmatic Response to Bronchial Challenge with Allergen-Mediators, Eicosanoids, Eosinophil and Neutrophil Constituents in the Blood and Urine

Delayed Asthmatic Response to Bronchial Challenge with Allergen-Mediators, Eicosanoids, Eosinophil and Neutrophil Constituents in the Blood and Urine

Interactive inhibitory effects of formoterol and montelukast on activated human neutrophils

Leukotriene B4 Potentiates CpG Signaling for Enhanced Cytokine Secretion by Human Leukocytes

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