16(R)-Hydroxyeicosatetraenoic Acid, a Novel Cytochrome P450 Product of Arachidonic Acid, Suppresses Activation of Human Polymorphonuclear Leukocytes and Reduces Intracranial Pressure in a Rabbit Model of Thromboembolic Stroke

@article{Bednar200016RHydroxyeicosatetraenoicAA,
  title={16(R)-Hydroxyeicosatetraenoic Acid, a Novel Cytochrome P450 Product of Arachidonic Acid, Suppresses Activation of Human Polymorphonuclear Leukocytes and Reduces Intracranial Pressure in a Rabbit Model of Thromboembolic Stroke},
  author={Martin M. Bednar and Cordell E. Gross and Sheila R. Russell and Susan P. Fuller and Terence Patrick Ahern and Diantha B. Howard and John R. Falck and Komandla Malla Reddy and Michael Balazy},
  journal={Neurosurgery},
  year={2000},
  volume={47},
  pages={1410-1419}
}
OBJECTIVEActivated polymorphonuclear leukocytes (PMNs) have been suggested to contribute to the development of increased intracranial pressure (ICP). We recently demonstrated that human PMNs produce a novel cytochrome P450-derived arachidonic acid metabolite, 16(R)-hydroxyeicosatetraenoic acid [16(R)-HETE], that modulates their function. It was thus of interest to examine this novel mediator in an acute stroke model. METHODS16-HETE was assessed initially in a variety of human PMN and platelet… 
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References

SHOWING 1-10 OF 66 REFERENCES
A neutrophil-derived cytochrome P450-dependent metabolite of arachidonic acid modulates neutrophil behavior.
TLDR
Peak 2 may modulate some activities of canine PMNs because the biologic activity of Peak 2 is opposite to that of LTB4, which promotes PMN aggregation and adhesion, and because L TB4 may be metabolized by a cytochrome P-450-dependent mixed function oxidase to less active metabolites, this enzyme system may play a central role in the control of PMN function.
The omega-hydroxylation of arachidonic acid by human polymorphonuclear leukocytes.
TLDR
It is concluded that the known LTB4 omega-monooxygenase is responsible for the formation of omega-hydroxy-arachidonate, one of four new metabolites formed in a previously described reverse-phase HPLC system.
The ω-hydroxylation of arachidonic acid by human polymorphonuclear leukocytes
TLDR
It is concluded that the known LTB4ω-monooxygenase is responsible for the formation of ω-hydroxy-arachidonate, which is unlikely, however, that significant concentrations of these metabolites are formed by activated polymorphonuclear leukocytes in vivo.
Quantitation of 20-hydroxy-5,8,11,14-eicosatetraenoic acid (20-HETE) produced by human polymorphonuclear leukocytes using electron capture ionization gas chromatography/mass spectrometry.
TLDR
The omega-hydroxy metabolite, 20- hydroxy-5,8,11,14-eicosatetraenoic acid (20-HETE) has recently been found to have interesting and diverse biological activities and accurate measurement of quantities of this metabolite using physical chemical methods is necessary to assess biosynthesis of this eicosanoid from endogenous arachidonic acid.
Cytochrome P-450-dependent oxidation of arachidonic acid to 16-, 17-, and 18-hydroxyeicosatetraenoic acids.
The role of neutrophils and platelets in a rabbit model of thromboembolic stroke.
TLDR
The results suggest that neutrophils may be important contributors to ischemia-induced brain injury whereas the role of platelets is more subtle.
IB4, a monoclonal antibody against the CD18 leukocyte adhesion protein, reduces intracranial pressure following thromboembolic stroke in the rabbit.
TLDR
It is concluded that blockade of the neutrophil adhesion protein, CD18, may contribute to a reduction in the intracranial pressure following cerebral ischemia and reperfusion, providing further evidence that activated neutrophils might contribute to cerebral edema.
...
1
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4
5
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