Novel polyisoprenyl phosphates block phospholipase D and human neutrophil activation in vitro and murine peritoneal inflammation in vivo.

ABSTRACT: Leukocyte production of reactive oxygen species (ROS) is an essential component of the antimicrobial armament mounted during host defense, but when released to the extracellular milieu ROS can also injure host tissues and provoke inflammation. Polyisoprenyl phosphates (PIPPs) are constituents of human leukocyte membranes that regulate pivotal intracellular enzymes, such as phospholipase D (PLD). We prepared new PIPP mimetics and studied their impact in vivo on leukocyte activation, including ROS generation, in acute inflammation. In a stereospecific and concentration-dependent manner, the PIPP mimetics directly regulated Streptomyces chromofuscus phospholipase D (sPLD) action. The IC(50) for a (Z)-isomer of endogenous presqualene diphosphate (PSDP) was 100 nM. Structure-activity relationsh

SUBMITTER: Levy BD 

PROVIDER: S-EPMC1440714 | biostudies-literature | 2005 Oct

REPOSITORIES: biostudies-literature