Arachidonate 15-lipoxygenase from human eosinophil-enriched leukocytes: Partial purification and properties

Sigal, Elliott; Grünberger, D.; Cashman, John R.; Craik, Charles S.; Caughey, George H.; Nade, Jay A.

doi:10.1016/0006-291x(88)90531-1

Cited by 51 publications

(20 citation statements)

References 12 publications

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“…The original studies on leu-kocyte 1 5-LO by Turk et al made the point that 1 5-LO activity correlated with the percentage of eosinophils in mixed leukocyte preparations (4). The amount of 1 5-LO activity determined by these investigators and confirmed by later studies in our group (6) can readily explain the levels of 1 5-LO activity reported in mixed leukocyte preparations. For example, 15-hydroxyicosatetraenoic acid (HETE) formation from eosinophils can be as high as 1,000 ng/106 cells (4,6,25).…”

Section: Resultssupporting

confidence: 77%

“…The amount of 1 5-LO activity determined by these investigators and confirmed by later studies in our group (6) can readily explain the levels of 1 5-LO activity reported in mixed leukocyte preparations. For example, 15-hydroxyicosatetraenoic acid (HETE) formation from eosinophils can be as high as 1,000 ng/106 cells (4,6,25). Therefore, a leukocyte preparation of 2 X IO' cells containing 4-8% eosinophils, which is within normal range after mononuclear cells are removed, can produce up to 1,600 ng of 15-HETE.…”

Section: Resultssupporting

confidence: 77%

“…This ability to perform lipid peroxidation is evident in multiple biological systems. For example, 1 5-LO activity has been identified by enzymatic assays in rabbit and human reticulocytes (2,3), in human leukocytes (4)(5)(6), in human lung (7), and in human airway epithelial cells (8). In the reticulocyte, the enzyme is believed to contribute to differentiation ofthat cell into a mature erythrocyte.…”

Section: Introductionmentioning

confidence: 99%

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Immunocytochemical localization of arachidonate 15-lipoxygenase in erythrocytes, leukocytes, and airway cells.

Nadel¹,

Conrad²,

Ueki³

et al. 1991

J. Clin. Invest.

107

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Section: Resultssupporting

confidence: 77%

Section: Resultssupporting

confidence: 77%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Immunocytochemical localization of arachidonate 15-lipoxygenase in erythrocytes, leukocytes, and airway cells.

Nadel¹,

Conrad²,

Ueki³

et al. 1991

J. Clin. Invest.

107

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“…Previous studies of AIA have also suggested deviations in the metabolism of arachidonic acid along pathways initiated by the 15-lipoxygenase (15-LO) enzyme, which incidentally is also very active in eosinophils [12]. It was thus reported that leukocytes from patients with AIA responded to an ex vivo aspirin challenge with increased formation of the main 15-LO product, 15S-hydroxy-eicosatetraenoic acid (15-HETE) [13], and this challenge has been suggested as an in vitro test of AIA [14].…”

Section: Introductionmentioning

confidence: 99%

The Influence of Aspirin on Release of Eoxin C4, Leukotriene C4 and 15-HETE, in Eosinophilic Granulocytes Isolated from Patients with Asthma

James

Daham

Backman

et al. 2013

Int Arch Allergy Immunol

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Background: The effect of aspirin on the release of key arachidonic acid metabolites in activated eosinophils from subjects with aspirin-intolerant asthma (AIA) has not been investigated previously, despite the characteristic eosinophilia in AIA. Methods: Peripheral blood eosinophils were isolated from four groups of subjects: healthy volunteers (HV; n = 8), mild asthma (MA; n = 8), severe asthma (SA; n = 9) and AIA (n = 7). In the absence or presence of lysine-aspirin, eosinophils were stimulated with arachidonic acid or calcium ionophore to trigger the 15-lipoxygenase-1 (15-LO) and 5-lipoxygenase (5-LO) pathways, respectively. 15(S)-hydroxy-eicosatetraenoic acid (15-HETE) and eoxin C₄ (EXC₄) were measured as 15-LO products and leukotriene (LT)C₄ as a product of the 5-LO pathway. Results: Activated eosinophils from patients with SA and AIA produced approximately five times more 15-HETE than eosinophils from HV or MA patients. In the presence of lysine-aspirin, eosinophils from AIA, MA and SA patients generated higher levels of 15-HETE than in the absence of lysine-aspirin. Furthermore, in the presence of lysine-aspirin, formation of EXC₄ was also significantly increased in eosinophils from AIA patients, and LTC₄ synthesis was increased both in AIA and SA patients. Conclusions: Taken together, this study shows an increased release of the recently discovered lipid mediator EXC₄, as well as the main indicator of 15-LO activity, 15-HETE, in activated eosinophils from severe and aspirin-intolerant asthmatics, and also elevated EXC₄ and LTC₄ formation in eosinophils from AIA patients after cellular activation in the presence of lysine-aspirin. The findings support a pathophysiological role of the 15-LO pathway in SA and AIA.

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“…However, this provides limited evidence for a role of the 12-LO, since known 15-lipoxygenases are soluble enzymes. For instance, more than 95% of the human eosinophil 15-LO activity was found in the lOOOOOxg supernatant [32]. In analogy, a possible platelet enzyme with o6-lipoxygenase activity would be expected to be found in the soluble fraction.…”

mentioning

confidence: 99%

On the mechanism of transcellular lipoxin formation in human platelets and granulocytes

Edenius

Stenke

Lindgren

1991

European Journal of Biochemistry

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Endogenous arachidonic acid was converted to lipoxins A4, B4 and (6S)-lipoxin A4, in ionophore-A23 187-stimulated mixtures of human platelets and granulocytes, while no lipoxins were formed when these cells were incubated separately. However, pure platelet suspensions transformed exogenous leukotriene A4 to lipoxins, including lipoxin A4 and (6S)-lipoxin A4, but not lipoxin B4. This compound was produced exclusively in the presence of granulocytes.A common unstable tetraene intermediate in lipoxin formation, 15-hydroxy-leukotriene A4 [5(6)-epoxy-l5-hydroxy-7,9,13-truns-11 -cis-eicosatetraenoic acid], was indicated by trapping experiments with methanol. Thus, identical profiles of less polar tetraene-containing derivatives were formed from leukotriene A4 in platelet suspensions, from exogenous 15-hydroxyeicosatetraenoic acid in granlocyte suspensions and from endogenous substrate in mixed platelet/granulocyte suspensions.Evidence for the involvement of 12-lipoxygenase in platelet-dependent lipoxin formation was obtained. Thus, lipoxin synthesis from leukotriene A4 and 12-hydroxyeicosatetraenoic acid production from arachidonic acid by human platelets was equally inhibited by 15-hydroxyeicosatetraenoic acid with 50% inhibition obtained at 7.0 pM and 8.2 pM, respectively. In experiments with subcellular preparations from platelets, lipoxin synthesis was observed in both the particulate and soluble fraction and was paralleled by the 12-lipoxygenase activity. Furthermore, lipoxin formation from leukotriene A4 in platelet sonicates was dose-dependently inhibited by exogenous arachidonic acid. Finally, 12-lipoxygenase-deficient platelets from a patient with chronic myelogenous leukemia were totally unable to produce lipoxins from exogenous or granulocyte-derived leukotriene A4.It is concluded that the transcellular lipoxin synthesis is dependent on the platelet 12-lipoxygenase and proceeds via the unstable intermediate, 15-hydroxy-leukotriene A4. This tetraene epoxide is transformed to lipoxin B4 by a granulocyte epoxide hydrolase activity or to lipoxin A4 and lipoxins A4/B4 isomers by enzymatic or nonenzymatic hydrolysisThe lipoxins (LX), a novel group of biologically active lipoxygenase (LO) products, are trihydroxylated arachidonic acid derivatives, containing a unique conjugated tetraene structure [l, 21. Diverse biological effects have been attributed Corrcspondencc to C. Edenius,

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Arachidonate 15-lipoxygenase from human eosinophil-enriched leukocytes: Partial purification and properties

Cited by 51 publications

References 12 publications

Immunocytochemical localization of arachidonate 15-lipoxygenase in erythrocytes, leukocytes, and airway cells.

Immunocytochemical localization of arachidonate 15-lipoxygenase in erythrocytes, leukocytes, and airway cells.

The Influence of Aspirin on Release of Eoxin C4, Leukotriene C4 and 15-HETE, in Eosinophilic Granulocytes Isolated from Patients with Asthma

On the mechanism of transcellular lipoxin formation in human platelets and granulocytes

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