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Esterified eicosanoids are acutely generated by 5-lipoxygenase in primary human neutrophils and in human and murine infection

Clark, Stephen Robert, Guy, Christopher J., Scurr, Martin J., Taylor, Philip Russel, Kift-Morgan, Ann Patricia, Hammond, Victoria Jayne, Thomas, Christopher P., Coles, Barbara, Roberts, Gareth Wyn, Eberl, Matthias, Jones, Simon Arnett, Topley, Nicholas, Kotecha, Sailesh and O'Donnell, Valerie Bridget 2011. Esterified eicosanoids are acutely generated by 5-lipoxygenase in primary human neutrophils and in human and murine infection. Blood 117 (6) , pp. 2033-2043. 10.1182/blood-2010-04-278887

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Abstract

5-Lipoxygenase (5-LOX) plays key roles in infection and allergic responses. Herein, four 5-LOX derived lipids comprising 5-hydroxyeicosatetraenoic acid (HETE) attached to phospholipids (PL), either phosphatidylethanolamine (PE) or phosphatidylcholine (PC) (18:0p/5-HETE-PE, 18:1p/5-HETE-PE, 16:0p/5-HETE-PE and 16:0a/5-HETE-PC), were identified in primary human neutrophils. They formed within 2 min in response to serum-opsonized Staphylococcus epidermidis (S. epidermidis) or fMLP, with priming by LPS, GM-CSF or cytochalasin D. Levels generated were similar to free 5-HETE (0.37 ± 0.14 ng vs 0.55 ± 0.18 ng/106 cells, esterified vs. free 5-HETE, respectively). They remained cell-associated, localizing to nuclear and extra-nuclear membrane, and were formed by fast esterification of newly synthesized free 5-HETE. Generation also required Ca2+, PLC, cPLA2, sPLA2, 5-LOX activating protein (FLAP) and MEK1. 5-HETE-PLs were detected in murine S. epidermidis peritonitis, paralleling neutrophil influx, and in effluent from Gram+ve human bacterial peritonitis. Formation of neutrophil extracellular traps (NETs) was significantly enhanced by 5-LOX inhibition, but attenuated by HETE-PE, while 5-HETE-PE enhanced superoxide and IL-8 generation. Thus, new molecular species of oxidized phospholipid formed by human neutrophils during bacterial infection are identified and characterized.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Systems Immunity Research Institute (SIURI)
Subjects: Q Science > QR Microbiology > QR180 Immunology
R Medicine > RC Internal medicine
Publisher: American Society of Hematology
ISSN: 0006-4971
Last Modified: 08 Aug 2019 20:38
URI: http://orca-mwe.cf.ac.uk/id/eprint/28358

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