Hepoxilins modulate second messenger systems in the human neutrophil.
In this chapter, we will review recent findings which implicate the hepoxilins as modulators of second messenger systems in the human neutrophil. We have shown that the hepoxilins affect calcium homeostasis in the cell and that they stimulate the release of arachidonic acid and diradylglycerol but not inositol phosphate indicating a mode of action for these 12-lipoxygenase metabolites that is independent of phospholipase C activation. In fact lipid analyses indicate that the phospholipid affected by the hepoxilins is phosphatidyl choline, and that this phospholipid is hydrolyzed by a phospholipase D. These findings indicate that the hepoxilins, which are formed by the platelet as well as the neutrophil, may affect neutrophil activation through a potential cell-cell interaction in the circulation or at pathologic sites to initiate or potentiate the inflammatory process.
Pace-Asciak
C R
CR
Research Institute, Hospital for Sick Children, Toronto, Canada.
Nigam
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D015126:8,11,14-Eicosatrienoic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D001095:Arachidonic Acids / Q000097:blood*; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D006801:Humans; D008954:Models, Biological; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D011433:Propranolol / Q000494:pharmacology; D015290:Second Messenger Systems
D001095:Arachidonic Acids; D005231:Fatty Acids, Unsaturated; C038243:8-hydroxy-11,12-epoxyeicosa-5,9,14-trienoic acid; D011433:Propranolol; D015126:8,11,14-Eicosatrienoic Acid