Aspirin-triggered 15-epi-lipoxin A4 (ATL) generation by human leukocytes and murine peritonitis exudates: Development of a specific 15-epi-LXA4 ELISA

Chiang, Nan; Takano, Tomoko; Clish, Clary B.; Petasis, Nicos A.; Tai, Hsin‐Hsiung; Serhan, Charles N.

doi:10.1016/s0090-6980(99)90421-5

Cited by 62 publications

(91 citation statements)

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“…In vivo, topical application of methyl esters of LXs and their stable analogs as well as the ATLs proved to be very effective for delivery. These methyl esters are converted to the corresponding free acids that are very likely in view of the present results to be responsible for the in vivo gene expression regulation and leukocyte trafficking impact (17)(18)(19).…”

Section: Discussionmentioning

confidence: 76%

Lipoxin A4 and Aspirin-Triggered 15-epi-Lipoxin A4 Inhibit Human Neutrophil Migration: Comparisons Between Synthetic 15 Epimers in Chemotaxis and Transmigration with Microvessel Endothelial Cells and Epithelial Cells

Fierro

Colgan

Bernasconi

et al. 2003

The Journal of Immunology

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106

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Lipoxins (LX) are bioactive eicosanoids that can be formed during cell to cell interactions in human tissues to self limit key responses in host defense and promote resolution. Aspirin treatment initiates biosynthesis of carbon 15 epimeric LXs, and both series of epimers (LX and aspirin-triggered 15-epi-LX) display counter-regulatory actions with neutrophils. In this study, we report that synthetic lipoxin A4 (LXA4) and 15-epi-LXA4 (i.e., 15(R)-LXA4 or aspirin-triggered LXA4) are essentially equipotent in inhibiting human polymorphonuclear leukocytes (PMN) in vitro chemotaxis in response to leukotriene B4, with the maximum inhibition (∼50% reduction) obtained at 1 nM LXA4. At higher concentrations, 15-epi-LXA4 proved more potent than LXA4 as its corresponding carboxyl methyl ester. Also, exposure of PMN to LXA4 and 15-epi-LXA4 markedly decreased PMN transmigration across both human microvessel endothelial and epithelial cells, where 15-epi-LXA4 was more active than LXA4 at “stopping” migration across epithelial cells. Differences in potency existed between LXA4 and 15-epi-LXA4 as their carboxyl methyl esters appear to arise from cell type-specific conversion of their respective carboxyl methyl esters to their corresponding carboxylates as monitored by liquid chromatography tandem mass spectrometry. Both synthetic LXA4 and 15-epi-LXA4 as free acids activate recombinant human LXA4 receptor (ALXR) to regulate gene expression, whereas the corresponding methyl ester of LXA4 proved to be a partial ALXR antagonist and did not effectively regulate gene expression. These results demonstrate the potent stereospecific actions shared by LXA4 and 15-epi-LXA4 for activating human ALXR-regulated gene expression and their ability to inhibit human PMN migration during PMN vascular as well as mucosal cell to cell interactions.

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Section: Discussionmentioning

confidence: 76%

Lipoxin A4 and Aspirin-Triggered 15-epi-Lipoxin A4 Inhibit Human Neutrophil Migration: Comparisons Between Synthetic 15 Epimers in Chemotaxis and Transmigration with Microvessel Endothelial Cells and Epithelial Cells

Fierro

Colgan

Bernasconi

et al. 2003

The Journal of Immunology

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106

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“…For example, ATL is generated in vivo from AA in healthy human subjects taking low-dose aspirin (33). As demonstrated in acute inflammation models (34,35), ATL is at least partially responsible for anti-neutrophilic and subsequent antiinflammatory, pro-resolving actions in humans of low-dose (75-81 mg) aspirin (29,33). These anti-neutrophilic recruitment and pro-resolving doses are significantly lower than the classical and generally used anti-rheumatic and anti-inflammatory doses (325-650 mg range) (36).…”

Section: Figurementioning

confidence: 99%

Pro-resolving actions and stereoselective biosynthesis of 18S E-series resolvins in human leukocytes and murine inflammation

Pillai²,

Recchiuti³

et al. 2011

J. Clin. Invest.

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255

305

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E-series resolvins are antiinflammatory and pro-resolving lipid mediators derived from the ω-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA) that actively clear inflammation to promote tissue homeostasis. Aspirin, in addition to exerting antithrombotic actions, also triggers the biosynthesis of these specialized pro-resolving mediators. Here, we used metabolomic profiling to investigate the biosynthesis of E-series resolvins with specific chiral chemistry in serum from human subjects and present evidence for new 18S series resolvins. Aspirin increased endogenous formation of 18S-hydroxyeicosapentaenoate (18S-HEPE) compared with 18R-HEPE, a known resolvin precursor. Human recombinant 5-lipoxygenase used both enantiomers as substrates, and recombinant LTA 4 hydrolase (LTA4H) converted chiral 5S(6)-epoxide-containing intermediates to resolvin E1 and 18S-resolvin E1 (RvE1 and 18S-RvE1, respectively). 18S-RvE1 bound to the leukocyte GPCRs ChemR23 and BLT1 with increased affinity and potency compared with the R-epimer, but was more rapidly inactivated than RvE1 by dehydrogenase. Like RvE1, 18S-RvE1 enhanced macrophage phagocytosis of zymosan, E. coli, and apoptotic neutrophils and reduced both neutrophil infiltration and proinflammatory cytokines in murine peritonitis. These results demonstrate two parallel stereospecific pathways in the biosynthesis of E-series resolvins, 18R-and 18S-, which are antiinflammatory, pro-resolving, and non-phlogistic and may contribute to the beneficial actions of aspirin and ω-3 polyunsaturated fatty acids.

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“…Examples are ions m/z 277 from RvD1 ( Figure 1 and Scheme 3), 261 from PD1 ( Figure 2, Scheme 4), 245 from 17-HpDHA (Figure 4 and Scheme 6), 195 from LTB 4 and 251 from LXA 4 [27,29], as well as ions 285 from 20-HDHA, 245 from 17-HDHA, 205 from 14-HDHA, and 165 from 11-HDHA (Table 1, Supplemental Figure 1 and Scheme 5). These fragmentation processes can also occur through ␥-ene-rearrangement if the cc segment has a ␥ double bond, which is at least the second double bond counted from the carboxyl group (for ion-trap MS/MS, unnecessary for triplequadrupole MS/MS, such as for 8 cc of 8,9-dihydroxyeicosatrienoic acids [27], and an ␣ allylic single bond [27,29].…”

Section: [Cc ϩ H] Ions In Ms/ms Of Lipid Mediatorsmentioning

confidence: 99%

“…This process also takes place through ␥-ene-rearrangement if the segment mm has a ␥-double bond and an ␣ allylic single bond. Examples are ions 141 from RvD1 ( Figure 1, Scheme 3), 193 from 11-HDHA, and 153 from 8-HDHA (Table 1, Supplemental Figure 1 and Scheme 5), as well as ions 145 of 5,6-diHETrE, 185 of 8,9-diHETrE, and 115 of both 5,6-diHETE and LXA 4 [27,29,30]. [mc Ϫ H] ions are also produced through an ␣-H-␤-ene rearrangement with shift of the ␣-H from segment mc to the ␥ position in segment mm whose ␣-bond is a vinyl single bond and ␤-bond is a double bond, such as ions m/z 261 from 16-HDHA (Table 1 (Table 1, Supplemental Figure 1 and Scheme 5), which are generated through a ␥-ene rearrangement and an ␣-H-␤-ene rearrangement, respectively.…”

Section: [Mc ϫ H] Ions In Ms/ms Of Lipid Mediatorsmentioning

confidence: 99%

Resolvin D1, protectin D1, and related docosahexaenoic acid-derived products: Analysis via electrospray/low energy tandem mass spectrometry based on spectra and fragmentation mechanisms

Hong

Lü

Rong

et al. 2007

J. Am. Soc. Mass Spectrom.

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Resolvin D1 (RvD1) and protectin D1 (Neuroprotectin D1, PD1/NPD1) are newly identified anti-inflammatory lipid mediators biosynthesized from docosahexaenoic acid (DHA). In this report, the spectra-structure correlations and fragmentation mechanisms were studied using electrospray low-energy collision-induced dissociation tandem mass spectrometry (MS/MS) for biogenic RvD1 and PD1, as well as mono-hydroxy-DHA and related hydroperoxy-DHA. The loss of H 2 O and CO 2 in the spectra indicates the number of functional group(s). Chain-cut ions are the signature of the positions and numbers of functional groups and double bonds. The observed chain-cut ion is equivalent to a hypothetical homolytic-segment (cc, cm, mc, or mm) with addition or extraction of up to 2 protons (H). The ␣-cleavage ions are equivalent to: [cc ϩ H], with H from the hydroxyl through a ␤-ene or ␥-ene rearrangement; [cm Ϫ 2H], with 2H from hydroxyls of PD1 through a ␥-ene rearrangement, or 1H from the hydroxyl and the other H from the ␣-carbon of mono-HDHA through an ␣-H-␤-ene rearrangement; [mc Ϫ H], with H from hydroxyl through a ␤-ene or ␥-ene rearrangement, or from the ␣-carbon through an ␣-H-␤-ene rearrangement; or [mm] through charge-direct fragmentations. The ␤-ene or ␥-ene facilitates the H shift to ␥ position and ␣-cleavage. Deuterium labeling confirmed the assignment of MS/MS ions and the fragmentation mechanisms. Based on the MS/MS spectra and fragmentation mechanisms, we identified RvD1, PD1, and mono-hydroxy-DHA products in human neutrophils and blood, trout head-kidney, and stroke-injury murine braintissue. (J Am Soc Mass Spectrom 2007, 18, 128 -144)

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Aspirin-triggered 15-epi-lipoxin A4 (ATL) generation by human leukocytes and murine peritonitis exudates: Development of a specific 15-epi-LXA4 ELISA

Cited by 62 publications

References 0 publications

Lipoxin A4 and Aspirin-Triggered 15-epi-Lipoxin A4 Inhibit Human Neutrophil Migration: Comparisons Between Synthetic 15 Epimers in Chemotaxis and Transmigration with Microvessel Endothelial Cells and Epithelial Cells

Lipoxin A4 and Aspirin-Triggered 15-epi-Lipoxin A4 Inhibit Human Neutrophil Migration: Comparisons Between Synthetic 15 Epimers in Chemotaxis and Transmigration with Microvessel Endothelial Cells and Epithelial Cells

Pro-resolving actions and stereoselective biosynthesis of 18S E-series resolvins in human leukocytes and murine inflammation

Resolvin D1, protectin D1, and related docosahexaenoic acid-derived products: Analysis via electrospray/low energy tandem mass spectrometry based on spectra and fragmentation mechanisms

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