Biosynthesis and biological activity of leukotriene B5

Terano, Takashi; Salmon, John A.; Moncada, Salvador

doi:10.1016/0090-6980(84)90075-3

Cited by 184 publications

(47 citation statements)

References 32 publications

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“…Subsequent world-wide epidemiological studies revealed the general existence of striking cardiovascular mortality differences between populations living on n-6 PUFAversus n-3 PUFA-rich diets ( 55 ). EPA was shown to compete with AA to yield less pro-aggregatory (TXA3 vs. TXA2) and less pro-infl ammatory eicosanoids (LTB5 vs. LTB4) via the COX-and LOX-dependent pathways ( 54,56 ). In contrast, PGI3, formed from EPA in the endothelium, acts with the same potency as a vasodilator and inhibitor of platelet results of the present study expand and specify the general hypothesis that dietary EPA/DHA supplementation causes pronounced changes in the endogenous eicosanoid profi le by providing alternative substrates for all three branches of the AA cascade.…”

Section: Discussionmentioning

confidence: 99%

Dietary omega-3 fatty acids modulate the eicosanoid profile in man primarily via the CYP-epoxygenase pathway

Fischer

Konkel

Mehling³

et al. 2014

Journal of Lipid Research

192

168

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This article is available online at http://www.jlr.org Cytochrome P450 (CYP) enzymes catalyze the formation of biologically active epoxy-and hydroxy-metabolites of long-chain PUFAs ( 1 ). Traditionally, and in line with the prevalence of n-6 PUFAs in the "Western diet", arachidonic acid (AA) (20:4 n-6) has been considered as the main precursor and the corresponding metabolites were categorized as a subclass of eicosanoids ( 2 ). CYP-eicosanoid formation is also known as the "third branch of the AA cascade," complementary to the previously discovered cyclooxygenase (COX)-and lipoxygenase (LOX)-initiated pathways of prostanoid and leukotriene formation ( 3, 4 ).Physiologically important AA-derived CYP-eicosanoids include a set of regio-and stereoisomeric epoxyeicosatrienoic acids (EETs) and 20-HETE ( 2, 5 ). EETs and 20-HETE play partially opposing roles in the regulation of vascular, renal, and cardiac function ( 6-9 ). The contribution of EETs to cardiovascular function is infl uenced by the soluble epoxide hydrolase (sEH) that metabolizes EETs to less potent dihydroxyeicosatrienoic acids (DHETs) ( 10 ). Imbalances in CYP-eicosanoid formation are linked to the development of endothelial dysfunction and hypertension; ischemia-induced injury of the heart, kidney and brain; infl ammatory disorders; and atherosclerosis (11)(12)(13)(14)(15)(16)(17).Recent studies demonstrated that the same CYP isoforms that epoxidize or hydroxylate AA, also effi ciently metabolize

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Section: Discussionmentioning

confidence: 99%

Dietary omega-3 fatty acids modulate the eicosanoid profile in man primarily via the CYP-epoxygenase pathway

Fischer

Konkel

Mehling³

et al. 2014

Journal of Lipid Research

192

168

View full text Add to dashboard Cite

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“…LTB 5 also binds to the LTB 4 receptor and it also activates leukocytes and promotes the development of inflammation, but it is far less damaging than LTB 4 . 19 Because reagents for an LTB5 assay did not exist, only LTB 4 was measured in the present study. The LTB4 level was significantly lower in the EPA group than in the non-EPA group (P Ͻ 0.01), indicating that EPA suppressed LTB 4 production.…”

Section: Discussionmentioning

confidence: 99%

Oral eicosapentaenoic acid for complications of bone marrow transplantation

Takatsuka

Takemoto

Iwata

et al. 2001

Bone Marrow Transplant

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Summary:The 'systemic inflammatory response syndrome' (SIRS) may represent the underlying cause of complications after bone marrow transplantation (BMT). This study was conducted to determine whether blocking the etiologic factors of SIRS could improve the complications of BMT. Sixteen consecutive patients with unrelated donors were allocated alternately to two groups. Seven patients received 1.8 g/day of eicosapentaenoic acid (EPA) orally from 3 weeks before to about 180 days after transplantation, while nine patients did not. These two groups were compared with respect to complications, survival, and various cytokines and factors causing vascular endothelial damage. All seven patients receiving EPA survived and only two had grade III graft-versus-host disease (GVHD). Among the nine patients not receiving EPA, three had grade III or IV GVHD. In addition, thrombotic microangiopathy developed in four patients and cytomegalovirus disease occurred in four. Five patients died in this group. The levels of leukotriene B 4 , thromboxane A 2 , and prostaglandin I 2 were significantly lower in patients receiving EPA than in those not receiving it (all P Ͻ 0.01). Cytokines such as tumor necrosis factor-␣, interferon-␥, and interleukin-10 were also significantly decreased by EPA (P Ͻ 0.05), as were factors causing vascular endothelial damage such as thrombomodulin and plasminogen activator inhibitor-1 (P Ͻ 0.05). The survival rate was significantly higher in the group given EPA (P Ͻ 0.01). EPA significantly reduced the complications of BMT, indicating that these complications may be manifestations of the systemic inflammatory response syndrome. Bone Marrow Transplantation (2001) 28, 769-774.

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“…With respect to leukotriene products of the 5-lipoxygenase pathway in leukocytes, LTB 5 , the dihydroxy derivative of 20:5n-3 formed from LTA 5 , is a weak and partial agonist compared with LTB 4 in eliciting inflammatory responses (11,22,23). The pentaenoic cysteinyl-leukotrienes are equiactive with their tetraenoic counterparts (11,24,25).…”

Section: Inhibition Of Neutrophil Leukotriene Bmentioning

confidence: 99%

Inhibition of Neutrophil Leukotriene B4 Production by a Novel Synthetic N-3 Polyunsaturated Fatty Acid Analogue, β-Oxa 21:3n-3

Robinson

Rathjen

Trout

et al. 2003

The Journal of Immunology

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We recently reported the synthesis and anti-inflammatory properties of a novel long chain polyunsaturated fatty acid (PUFA) with an oxygen atom in the β-position, β-oxa-21:3 n-3 (Z,Z,Z)-(octadeca-9,12,15-trienyloxy) acetic acid). Our data, from studies aimed at elucidating the mechanism of its action, show that pretreatment of human neutrophils with the β-oxa-PUFA substantially depresses the production of leukotriene B4 (LTB4) in response to calcium ionophore, A23187, comparable to standard leukotriene inhibitors such as zileuton and nordihydroguaiaretic acid. Interestingly, the n-6 equivalent, β-oxa 21:3 n-6, is also a strong inhibitor of LTB4 production. In contrast, naturally occurring PUFA only slightly reduce, for eicosapentaenoic (20:5n-3) and docosahexaenoic (22:6n-3) acids, or increase, for arachidonic acid (20:4n-6), the formation of LTB4. The parent β-oxa-21:3n-3 molecule, rather than its derivatives (methyl ester, saturated, monohydroperoxy, or monohydroxy forms), is exclusively responsible for attenuation of LTB4 formation. β-Oxa-21:3n-3 inhibits the conversion of [3H]20:4n-6 to [3H]5-hydroxyeicosatetraenoic acid and [3H]LTB4 by neutrophils in the presence of calcium ionophore and also suppresses the activity of purified 5-lipoxygenase, but not cyclooxygenase 1 and 2. β-Oxa-21:3n-3 is taken up by neutrophils and incorporated into phospholipids and neutral lipids. In the presence of calcium ionophore, the leukocytes convert a marginal amount of β-oxa-21:3n-3 to a 16-monohydroxy-β-oxa-21:3n-3 derivative. After administration to rodents by gavage or i.p. injection, β-oxa-21:3n-3 is found to be incorporated into the lipids of various tissues. Thus, β-oxa-21:3n-3 has the potential to be used in the treatment of inflammatory diseases, which are mediated by products of the lipoxygenase pathway.

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Biosynthesis and biological activity of leukotriene B5

Cited by 184 publications

References 32 publications

Dietary omega-3 fatty acids modulate the eicosanoid profile in man primarily via the CYP-epoxygenase pathway

Dietary omega-3 fatty acids modulate the eicosanoid profile in man primarily via the CYP-epoxygenase pathway

Oral eicosapentaenoic acid for complications of bone marrow transplantation

Inhibition of Neutrophil Leukotriene B4 Production by a Novel Synthetic N-3 Polyunsaturated Fatty Acid Analogue, β-Oxa 21:3n-3

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