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

被引：74

作者：

Clark, Stephen R. ^{[1
]}

Guy, Christopher J. ^{[1
]}

Scurr, Martin J. ^{[1
]}

Taylor, Philip R. ^{[1
]}

Kift-Morgan, Ann P. ^{[1
]}

Hammond, Victoria J. ^{[1
]}

Thomas, Christopher P. ^{[1
]}

Coles, Barbara ^{[1
]}

Roberts, Gareth W. ^{[2
]}

Eberl, Matthias ^{[1
]}

Jones, Simon A. ^{[1
]}

Topley, Nicholas ^{[1
]}

Kotecha, Sailesh ^{[3
]}

O'Donnell, Valerie B. ^{[1
]}

机构：

[1] Cardiff Univ, Dept Infect Immun & Biochem, Sch Med, Cardiff CF14 4XN, S Glam, Wales

[2] Cardiff Univ, Inst Nephrol, Sch Med, Cardiff CF14 4XN, S Glam, Wales

[3] Cardiff Univ, Dept Child Hlth, Sch Med, Cardiff CF14 4XN, S Glam, Wales

来源：

BLOOD | 2011年 / 117卷 / 06期

基金：

英国惠康基金;

关键词：

ACTIVATED HUMAN PLATELETS; ARACHIDONIC-ACID; OXIDIZED PHOSPHOLIPIDS; PERITONEAL-DIALYSIS; INNATE IMMUNE; LIPOXYGENASE; INFLAMMATION; INHIBITION; ATHEROSCLEROSIS; LEUKOTRIENES;

D O I：

10.1182/blood-2010-04-278887

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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 (PLs), either phosphatidylethanolamine (PE) or phosphatidylcholine (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 minutes in response to serum-opsonized Staphylococcus epidermidis or f-methionine-leucine-phenylalanine, with priming by lipopolysaccharide, granulocyte macrophage colony-stimulating factor, or cytochalasin D. Levels generated were similar to free 5-HETE (0.37 +/- 0.14 ng vs 0.55 +/- 0.18 ng/10(6) cells, esterified vs free 5-HETE, respectively). Theyremained cell associated, localizing to nuclear and extranuclear membrane, and were formed by fast esterification of newly synthesized free 5-HETE. Generation also required Ca2+, phospholipase C, cytosolic and secretory phospholipase A(2), 5-LOX activating protein, and mitogen-activated protein kinase/extracellular signal-regulated kinase kinase 1. 5-HETE-PLs were detected in murine S epidermidis peritonitis, paralleling neutrophil influx, and in effluent from Gram-positive human bacterial peritonitis. Formation of neutrophil extracellular traps was significantly enhanced by 5-LOX inhibition but attenuated by HETE-PE, whereas 5-HETE-PE enhanced superoxide and interleukin-8 generation. Thus, new molecular species of oxidized PL formed by human neutrophils during bacterial infection are identified and characterized. (Blood. 2011; 117(6): 2033-2043)

引用

页码：2033 / 2043

页数：11

共 39 条

[1] 5-LIPOXYGENASE-ACTIVATING PROTEIN STIMULATES THE UTILIZATION OF ARACHIDONIC-ACID BY 5-LIPOXYGENASE [J].

ABRAMOVITZ, M ;

WONG, E ;

COX, ME ;

RICHARDSON, CD ;

LI, C ;

VICKERS, PJ .

EUROPEAN JOURNAL OF BIOCHEMISTRY, 1993, 215 (01) :105-111

[2]

[Anonymous], 2010, J Vis Exp, DOI DOI 10.3791/1724)

[3] Preferential esterification of endogenously formed 5-hydroxyeicosatetraenoic acid to phospholipids in activated polymorphonuclear leukocytes [J].

Arai, M ;

Imai, H ;

Metori, A ;

Nakagawa, Y .

EUROPEAN JOURNAL OF BIOCHEMISTRY, 1997, 244 (02) :513-519

[4]

Bailie MB, 1996, J IMMUNOL, V157, P5221

[5] STIMULATION BY LIPOXYGENASE PRODUCTS OF SUPEROXIDE ANION PRODUCTION IN FMLP-TREATED NEUTROPHILS [J].

BECKMAN, JK ;

GAY, JC ;

BRASH, AR ;

LUKENS, JN ;

OATES, JA .

LIPIDS, 1985, 20 (05) :318-321

[6] Opposing and hierarchical roles of leukotrienes in local innate immune versus vascular responses in a model of sepsis [J].

Benjamim, CF ;

Canetti, C ;

Cunha, FQ ;

Kunkel, SL ;

Peters-Golden, M .

JOURNAL OF IMMUNOLOGY, 2005, 174 (03) :1616-1620

[7] MEK-1/2 inhibition prevents 5-lipoxygenase translocation in N-formylpeptide-challenged human neutrophils [J].

Boden, SE ;

Bertsche, T ;

Ammon, HPT ;

Safayhi, H .

INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, 2000, 32 (10) :1069-1074

[8] SELECTIVE INCORPORATION OF (15S)-HYDROXYEICOSATETRAENOIC ACID IN PHOSPHATIDYLINOSITOL OF HUMAN NEUTROPHILS - AGONIST-INDUCED DEACYLATION AND TRANSFORMATION OF STORED HYDROXYEICOSANOIDS [J].

BREZINSKI, ME ;

SERHAN, CN .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1990, 87 (16) :6248-6252

[9] Characterization of nitric oxide consumption pathways by normal, chronic granulomatous disease and myeloperoxidase-deficient human neutrophils1 [J].

Clark, SR ;

Coffey, MJ ;

Maclean, RM ;

Collins, PW ;

Lewis, MJ ;

Cross, AR ;

O'Donnell, VB .

JOURNAL OF IMMUNOLOGY, 2002, 169 (10) :5889-5896

[10] Platelet TLR4 activates neutrophil extracellular traps to ensnare bacteria in septic blood [J].

Clark, Stephen R. ;

Ma, Adrienne C. ;

Tavener, Samantha A. ;

McDonald, Braedon ;

Goodarzi, Zahra ;

Kelly, Margaret M. ;

Patel, Kamala D. ;

Chakrabarti, Subhadeep ;

McAvoy, Erin ;

Sinclair, Gary D. ;

Keys, Elizabeth M. ;

Allen-Vercoe, Emma ;

DeVinney, Rebekah ;

Doig, Christopher J. ;

Green, Francis H. Y. ;

Kubes, Paul .

NATURE MEDICINE, 2007, 13 (04) :463-469

← 1 2 3 4 →