Formation of Hydroxyeicosatetraenoic Acids (HETE) in Blood From Adults Versus Neonates: Reduced Production of 12-HETE in Cord Blood

Walenga, Ronald W.; Sunderji, Shiraz; Stuart, Marie J.

doi:10.1203/00006450-198811000-00005

Cited by 13 publications

(3 citation statements)

References 12 publications

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“…To also test the hypothesis that 12/15-LO products can directly stimulate monocyte adhesion, B6 control and LOKO EC were treated for 4 h with 100 nM 12S-HETE and then used in an adhesion assay. This concentration of 12S-HETE is believed to be within the physiological range found in blood (see "Discussion") (37)(38)(39)(40)(41)(42). We performed dose-response studies with exogenous 12S-HETE on monocyte/EC adhesion and found, within a dose range of 1-500 nM 12S-HETE, that 100 nM 12S-HETE was the lowest concentration that provided a significant increase in monocyte adhesion to B6 control EC (data not shown).…”

Section: /15-lo Products Directly Stimulate Monocyte/endothelialmentioning

confidence: 99%

12/15-Lipoxygenase Activity Mediates Inflammatory Monocyte/Endothelial Interactions and Atherosclerosis in Vivo

Reilly

Srinivasan

Hatley

et al. 2004

Journal of Biological Chemistry

139

109

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We have shown that the 12/15-lipoxygenase (12/15-LO) product 12S-hydroxyeicosatetraenoic acid increases monocyte adhesion to human endothelial cells (EC) in vitro. Recent studies have implicated 12/15-LO in mediating atherosclerosis in mice. We generated transgenic mice on a C57BL/6J (B6) background that modestly overexpressed the murine 12/15-LO gene (designated LOTG). LOTG mice had 2.5-fold elevations in levels of 12S-hydroxyeicosatetraenoic acid and a 2-fold increase in expression of 12/15-LO protein in vivo. These mice developed spontaneous aortic fatty streak lesions on a chow diet. Thus, we examined effects of 12/15-LO expression on early events leading to atherosclerosis in these mice. We found that, under basal unstimulated conditions, LOTG EC bound more monocytes than B6 control EC (18 ؎ 2 versus 7 ؎ 1 monocytes/field, respectively; p < 0.0001). Inhibition of 12/15-LO activity in LOTG EC using a 12/15-LO ribozyme completely blocked monocyte adhesion in LOTG mice. Thus, 12/15-LO activity is required for monocyte/EC adhesion in the vessel wall. Expression of ICAM-1 in aortic endothelia of LOTG mice was increased severalfold. VCAM-1 expression was not changed. In a series of blocking studies, antibodies to ␣ 4 and ␤ 2 integrins in WEHI monocytes blocked monocyte adhesion to both LOTG and B6 control EC. Inhibition of ICAM-1, VCAM-1, and connecting segment-1 fibronectin in EC significantly reduced adhesion of WEHI monocytes to LOTG EC. In summary, these data indicate that EC from LOTG mice are "pre-activated" to bind monocytes. Monocyte adhesion in LOTG mice is mediated through ␤ 2 integrin and ICAM-1 interactions as well as through VLA-4 and connecting segment-1 fibronectin/ VCAM-1 interactions. Thus, 12/15-LO mediates monocyte/EC interactions in the vessel wall in atherogenesis at least in part through molecular regulation of expression of endothelial adhesion molecules.Murine 12/15-lipoxygenase (12/15-LO) 1 incorporates molecular oxygen in a stereospecific manner into arachidonic and linoleic acids to generate 12S-and 15S-hydroxyeicosatetraenoic acids (12S-HETE) and 13S-hydroxyoctadecadienoic acid (13S-HODE) (1-3). Murine 12/15-LO is similar biochemically and structurally to the porcine leukocyte-type 12-LO and human 15-LO enzymes (2-4). There also exists a murine platelet 12-LO, which utilizes arachidonic acid solely as a substrate to generate 12S-HETE (4, 5).The exact biologic functions of 12/15-LO are unknown. However, considerable evidence exists to support a role for 12/ 15-LO in promoting both diabetes and atherosclerosis (6 -9). Nadler and co-workers (6) have shown that mice deficient in 12/15-LO are protected from development of low dose streptozotocin-induced diabetes. We have recently shown that diabetic db/db mice produce significant quantities of 12S-HETE in vivo (10). Importantly, using a catalytic ribozyme to inactivate 12/ 15-LO mRNA, we have shown that disruption of 12/15-LO mRNA in diabetic db/db mice blocks monocyte adhesion (10). Striking evidence for the role of 12/15-LO in atherogenes...

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Section: /15-lo Products Directly Stimulate Monocyte/endothelialmentioning

confidence: 99%

12/15-Lipoxygenase Activity Mediates Inflammatory Monocyte/Endothelial Interactions and Atherosclerosis in Vivo

Reilly

Srinivasan

Hatley

et al. 2004

Journal of Biological Chemistry

139

109

View full text Add to dashboard Cite

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“…The in vitro stimulation of whole blood by ionophore A23187 generated large amounts of leukotrienes (LTs), but their analysis also requires tedious extraction and purification, with addition of radioactive internal standard to evaluate recovery, followed by solid-phase extraction or on-line extraction procedure prior to reverse-phase high-performance liquid chro-matography analysis (RP-HPLC) (9 -11). In addition to LTs, monohydroxyeicosatetraenoic acids (HETEs) such as 5-HETE and 12-HETE are generated in large amounts by white blood cells and platelets, respectively, after whole blood stimulation (10,(12)(13)(14) at levels ranging from 0.3 to 4.0 M after whole blood stimulation (15,16). Therefore, we focused on HETEs which are less polar and more stable than LTB 4 and cysteinyl LTs and developed a method to measure 5-HETE which is biosynthesized at the first step of the arachidonic acid cascade during the inflammation process mediated by the 5-lipoxygenase pathway.…”

mentioning

confidence: 99%

A Method for the Measurement of Plasma Hydroxyeicosatetraenoic Acid Levels

Chavis

Fraissinet

Chanez

et al. 1999

Analytical Biochemistry

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“…During this period, physiological levels of some coagulation factors and anticoagulant proteins are low, and platelet function shows some differences from adult platelets [1][2][3][4][5][6][7][8][9]. However, there is no real evidence that these relative deficits are clinically significant in the healthy newborn [1,3,10].…”

Section: Introductionmentioning

confidence: 99%

Platelet Activation during the Early Neonatal Period

İrken

Mutafoglu²,

Olgun³

et al. 1998

Neonatology

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The first week of life is a time when hereditary or more frequently acquired factors lead to some important differences in the hemostatic mechanism of the newborn. It has been well known that ill neonates are prone to both hemorrhage and thrombosis. The aim of this study was to answer the question of whether there is a difference in platelet activation in healthy neonates during the first days of life that may contribute to both hemorrhage and thrombosis in the presence of additional pathologic insults. Platelet activation was determined with flow cytometry using monoclonal antibodies in 63 healthy children (29 neonates, 17 infants, and 17 older children). There was no significant difference in platelet activation among these three age groups (p > 0.05). In addition, platelet activation did not show any significant relationship to age, sex, mode of delivery, or blood bilirubin concentration (p > 0.05). It has been previously reported that platelet activation occurs at the time of birth. We could not find any evidence that healthy newborns during the first 3 days of life exhibit increased platelet activation. Further studies on platelet activation in ill neonates will help to clarify whether platelet activation plays a role in the pathogenesis of thrombotic and/or hemorrhagic disorders.

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Formation of Hydroxyeicosatetraenoic Acids (HETE) in Blood From Adults Versus Neonates: Reduced Production of 12-HETE in Cord Blood

Cited by 13 publications

References 12 publications

12/15-Lipoxygenase Activity Mediates Inflammatory Monocyte/Endothelial Interactions and Atherosclerosis in Vivo

12/15-Lipoxygenase Activity Mediates Inflammatory Monocyte/Endothelial Interactions and Atherosclerosis in Vivo

A Method for the Measurement of Plasma Hydroxyeicosatetraenoic Acid Levels

Platelet Activation during the Early Neonatal Period

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