To determine the relationship of polyisoprenyl phosphate (PIPP) remodeling
and signaling to the activation state of human neutrophils (PMN), we examin
ed the impact of leukotriene B-4 (LTB4) on the conversion of a unique bioac
tive isoprenoid (presqualene diphosphate: PSDP), recently identified as a n
ovel endogenous signaling molecule. LTB4 initiated rapid decrements in tota
l PSDP that were concurrent with the respiratory burst (e.g., O-2(-) format
ion). PSDP was identified in nuclear (39%)-, granule (36%)-, and plasma mem
brane (16%)-containing fractions of PMN. LTB4 receptor (BLT) activation led
to a decrease in nuclear PSDP and concomitant increase in granule-associat
ed PSDP. In addition, PMN nuclei displayed PSDP associated with chromatin a
s established by mass spectrometry, Together, these results indicate that P
SDP is present in membranes and receptor activation rapidly initiates subce
llular PIPP remodeling (i.e., conversion) and distribution predominantly to
granule membranes. Moreover, identification of nuclear PSDP provides the b
asis for novel roles for PIPP and PSDP in nuclear-associated signaling even
ts. (C) 2000 Academic Press.