title: Polyisoprenyl phosphate signaling: topography in human neutrophils.
abstract: To determine the relationship of polyisoprenyl phosphate (PIPP) remodeling and signaling to the activation state of human neutrophils (PMN), we examined the impact of leukotriene B(4) (LTB(4)) on the conversion of a unique bioactive isoprenoid (presqualene diphosphate: PSDP), recently identified as a novel endogenous signaling molecule. LTB(4) initiated rapid decrements in total PSDP that were concurrent with the respiratory burst (e.g., O(-2) formation). PSDP was identified in nuclear (39%)-, granule (36%)-, and plasma membrane (16%)-containing fractions of PMN. LTB(4) receptor (BLT) activation led to a decrease in nuclear PSDP and concomitant increase in granule-associated PSDP. In addition, PMN nuclei displayed PSDP associated with chromatin as established by mass spectrometry. Together, these results indicate that PSDP is present in membranes and receptor activation rapidly initiates subcellular PIPP remodeling (i.e., conversion) and distribution predominantly to granule membranes. Moreover, identification of nuclear PSDP provides the basis for novel roles for PIPP and PSDP in nuclear-associated signaling events.
authors.affiliation: Center for Experimental Therapeutics and Reperfusion Injury, Department of Internal Medicine, Brigham and Women's Hospital and Harvard Medical School, 75 Francis Street, Boston, Massachusetts, 02115, USA.
authors.forename: B D
authors.initials: BD
authors.lastname: Levy
authors.forename: C N
authors.initials: CN
authors.lastname: Serhan
mesh_terms: D001692:Biological Transport / Q000187:drug effects; D002458:Cell Fractionation; D002462:Cell Membrane / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002843:Chromatin / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D003571:Cytochalasin B / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007975:Leukotriene B4 / Q000494:pharmacology; D013058:Mass Spectrometry; D018375:Neutrophil Activation / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism*; D011106:Polyisoprenyl Phosphates / Q000378:metabolism / Q000494:pharmacology*; D018102:Receptors, Leukotriene B4 / Q000378:metabolism; D016897:Respiratory Burst / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects*; D013481:Superoxides / Q000378:metabolism
chemical_list: D002843:Chromatin; D004791:Enzyme Inhibitors; D011106:Polyisoprenyl Phosphates; D018102:Receptors, Leukotriene B4; D013481:Superoxides; D007975:Leukotriene B4; C017672:presqualene pyrophosphate; D003571:Cytochalasin B