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Dihydroxyoctadecamonoenoate esters inhibit the neutrophil respiratory burst

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Abstract

The leukotoxins [9(10)-and 12(13)-EpOME] are produced by activated inflammatory leukocytes such as neutrophils. High EpOME levels are observed in disorders such as acute respiratory distress syndrome and in patients with extensive burns. Although the physiological significance of the EpOMEs remains poorly understood, in some systems, the EpOMEs act as a protoxin, with their corresponding epoxide hydrolase metabolites, 9,10-and 12,13-DiHOME, specifically exerting toxicity. Both the EpOMEs and the DiHOMEs were also recently shown to have neutrophil chemotactic activity. We evaluated whether the neutrophil respiratory burst, a surge of oxidant production thought to play an important role in limiting certain bacterial and fungal infections, is modulated by members of the EpOME metabolic pathway. We present evidence that the DiHOMEs suppress the neutrophil respiratory burst by a mechanism distinct from that of respiratory burst inhibitors such as cyclosporin H or lipoxin A4, which inhibit multiple aspects of neutrophil activation.

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Abbreviations

AMP:

adenosine monophosphate

ARDS:

acute respiratory distress syndrome

ATCC:

American Type Culture Collection

CHAPS:

3-[(3-cholamidopropyl) dimethylammonio]-1-propanesulfonic acid

DHET:

dihydroxyeicosatetraenoic acid

DiEpEDEs:

diepoxyeicosadienoates

DiHOME:

dihydroxyoctadecenoic acid

EDTA:

ethylenediamine tetra-acetic acid

EET:

epoxyicosatetraenoic acid

EGTA:

ethylene glycol tetraacetic acid

EpETEs:

epoxyeicosatrienoates

EpOME:

epoxyoctadecenoic acid

fMLF:

N-formyl-methionyl-leucyl-phenylalanine

GC/MS:

gas chromatography/mass spectroscopy

HBSS:

Hank’s buffered salt solution

15-HETE:

hydroxyeicosatetraenoic acid

8-HETE:

methyl 8-hydroxy-eicosatetraenoate

HEPES:

N-(2-hydroxyethyl) piperazine-N’-(2-ethanesulphonic acid)

HL-60:

human leukaemia cell line

HPLC:

high performance liquid chromatography

IEF:

isoelectric focusing

NADPH:

nictonamide adenine dinucleotide

NEPHGE:

non-equilibrium pH gradient electrophoresis

NMR:

nuclear magnetic resonance

PAF:

platelet-activating factor

PBS:

phosphate buffered saline

PMA:

phorbolmyristate acetate

PVDF:

polyvinylidene fluoride

sEH:

soluble epoxide hydrolase

TLC:

thin layer chromatography

UV:

ultra-violet

WST-1:

2-(4-iodophenyl)-3-(4-nitrophenyl)-5-(2,4-disulphophenyl)-2H-tetrazolium monosodium salt.

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Thompson, D.A., Hammock, B.D. Dihydroxyoctadecamonoenoate esters inhibit the neutrophil respiratory burst. J Biosci 32, 279–291 (2007). https://doi.org/10.1007/s12038-007-0028-x

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