Leukotrienes: Mediators that have been typecast as villains

Flamand, Nicolas; Mancuso, Peter; Serezani, C. Henrique; Brock, Thomas G.

doi:10.1007/s00018-007-7228-2

Cited by 60 publications

(65 citation statements)

References 171 publications

(160 reference statements)

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“…These conditions were excluded in our study. Additionally LT B4 has been described to be overproduced in ulcerative colitis, Crohn's disease, inflammatory bowel disease, rheumatoid arthritis and other disorders 18) , associated with antineutrophil cytoplasmic antibody (ANCA) positivity, such as disorders due to silica and asbestos exposure 30,31) . Further studies are needed to elucidate any possible relationships.…”

Section: Discussionmentioning

confidence: 99%

“…LTs are analogous to hormones that act locally and are considered as chemical messengers that transmit signals from immune system cells to essentially all other types of cells in the surrounding tissues 18) . LT B4 is best known for its role in initiating the inflammatory response, produced by leukocytes (e.g.…”

Section: Introductionmentioning

confidence: 99%

“…macrophages) residing in the tissue in response to stimuli like infection or stress. It has been found to be overproduced in ulcerative colitis, Crohn's disease, inflammatory bowel disease, rheumatoid arthritis and other disorders 18) .…”

Section: Introductionmentioning

confidence: 99%

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Leukotrienes B4, C4, D4 and E4 in the Exhaled Breath Condensate (EBC), Blood and Urine in Patients with Pneumoconiosis

Pelclová¹,

Fenclová²,

Vlčková³

et al. 2012

Ind Health

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Leukotrienes (LTs) are involved in the pathogenesis of lung fibrosis and were increased in exhaled breath condensate (EBC) of the patients with pneumoconiosis. However the possible influence of extra-pulmonary disorders on the EBC markers is not known. Therefore in parallel with EBC, LTs' levels in the plasma and urine were measured in patients with pneumoconiosis (45 × asbestos exposure, 37 × silica exposure) and in 27 controls. Individual LTs B4, C4, D4 and E4 were measured by liquid chromatography − electrospray ionization − tandem mass spectrometry (LC-ESI-MS/MS). In EBC, LT D4 and LT E4 were increased in both groups of patients (p<0.001 and p<0.05), comparing with the controls. Both LT B4 and cysteinyl LTs were elevated in asbestosexposed subjects (p<0.05). Asbestosis with more severe radiological signs (s1/s2-t3/u2) and lung functions impairment has shown higher cysteinyl LTs and LT C4 in the EBC (p<0.05) than mild asbestosis (s1/s0-s1/s1). In addition, in the subjects with asbestosis, cysteinyl LTs in EBC correlated with TLC (−0.313, p<0.05) and TLCO/Hb (−0.307, p<0.05), and LT C4 with TLC (−0.358, p<0.05). In pneumoconioses, EBC appears the most useful from the 3 fluids studied.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Leukotrienes B4, C4, D4 and E4 in the Exhaled Breath Condensate (EBC), Blood and Urine in Patients with Pneumoconiosis

Pelclová¹,

Fenclová²,

Vlčková³

et al. 2012

Ind Health

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“…LTs are chemical messengers that transmit signals from cells of the immune system to virtually all cell types in the surrounding tissue (17). LTs are divided into two large families, LTB 4 and cysteinylLTs, which activate distinct receptors in immune cells.…”

mentioning

confidence: 99%

Leukotriene B4 Modulates P2X7 Receptor–MediatedLeishmania amazonensisElimination in Murine Macrophages

Chaves

Marques-da-Silva

Monteiro

et al. 2014

The Journal of Immunology

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ATP is an important signaling molecule in the immune system, and it is able to bind the P2X7 purinergic receptor. Recently, our group showed that ATP-treated macrophages eliminate Leishmania amazonensis. It has been reported that leukotriene B4 (LTB4) reduces the parasitic load of infected macrophages. Additionally, it has been demonstrated that the P2X7 receptor can induce PLA2 activation and arachidonic acid mobilization. Based on these findings, we investigated whether LTB4 is produced upon P2X7 receptor activation and examined whether LTB4 modulates parasite elimination. Using macrophages lacking the P2X7 receptor, we observed that ATP was not able to reduce L. amazonensis load. This result suggests a role of the P2X7 purinergic receptor in parasite elimination. In addition, ATP was sufficient to induce LTB4 release from infected control macrophages but not from macrophages lacking the P2X7 receptor. Moreover, we found that ATP failed to decrease the parasitic load in 5-lipoxygenase (LO)–deficient macrophages. Treatment with the 5-LO inhibitor AA861 also impairs the ATP effect on parasitic loads. Furthermore, macrophages from 5-LO knockout mice eliminated L. amazonensis in the presence of exogenous LTB4, and macrophages obtained from P2X7 receptor knockout mice eliminated L. amazonensis when incubated with ionomycin. Finally, we demonstrated that in the presence of CP105696, an antagonist for LTB4 high-affinity receptor, ATP was not able to reduce parasitic load. These results indicate that P2X7 receptor activation leads to LTB4 formation, which is required for L. amazonensis elimination.

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“…The Cys-LTs are potent vasoconstrictors of both venous and arterial smooth muscle (105,142), and are also reported to produce vascular leak and vasogenic edema (36). Furthermore, pharmacological inhibition of Cys-LT receptors attenuates pathological outcomes in a rodent model of focal cerebral ischemia, suggesting roles for Cys-LTs in mediating ischemic injury (31,44). Like LTB 4 , Cys-LTs also operate as potent activators and chemoattractants for leukocytes, particularly eosinophils and monocytes, thereby indirectly propagating inflammation and oxidative stress (44).…”

Section: Hydroperoxy-and Hydroxy-eicosatetraenoic Acidsmentioning

confidence: 99%

Significance of Brain Tissue Oxygenation and the Arachidonic Acid Cascade in Stroke

Rink

Khanna

2011

Antioxidants & Redox Signaling

166

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The significance of the hypoxia component of stroke injury is highlighted by hypermetabolic brain tissue enriched with arachidonic acid (AA), a 22:6n-3 polyunsaturated fatty acid. In an ischemic stroke environment in which cerebral blood flow is arrested, oxygen-starved brain tissue initiates the rapid cleavage of AA from the membrane phospholipid bilayer. Once free, AA undergoes both enzyme-independent and enzyme-mediated oxidative metabolism, resulting in the formation of number of biologically active metabolites which themselves contribute to pathological stroke outcomes. This review is intended to examine two divergent roles of molecular dioxygen in brain tissue as (1) a substrate for life-sustaining homeostatic metabolism of glucose and (2) a substrate for pathogenic metabolism of AA under conditions of stroke. Recent developments in research concerning supplemental oxygen therapy as an intervention to correct the hypoxic component of stroke injury are discussed. Antioxid. Redox Signal. 14, 1889-1903. Brain Oxygen Consumption and Regulation

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Leukotrienes: Mediators that have been typecast as villains

Cited by 60 publications

References 171 publications

Leukotrienes B4, C4, D4 and E4 in the Exhaled Breath Condensate (EBC), Blood and Urine in Patients with Pneumoconiosis

Leukotrienes B4, C4, D4 and E4 in the Exhaled Breath Condensate (EBC), Blood and Urine in Patients with Pneumoconiosis

Leukotriene B4 Modulates P2X7 Receptor–MediatedLeishmania amazonensisElimination in Murine Macrophages

Significance of Brain Tissue Oxygenation and the Arachidonic Acid Cascade in Stroke

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