title: Molecular control of PtdIns(3,4,5)P3 signaling in neutrophils.
abstract: Neutrophils play critical roles in innate immunity and host defense. However, excessive neutrophil accumulation or hyper-responsiveness of neutrophils can be detrimental to the host system. Thus, the response of neutrophils to inflammatory stimuli needs to be tightly controlled. Many cellular processes in neutrophils are mediated by localized formation of an inositol phospholipid, phosphatidylinositol (3,4,5)-trisphosphate (PtdIns(3,4,5)P3), at the plasma membrane. The PtdIns(3,4,5)P3 signaling pathway is negatively regulated by lipid phosphatases and inositol phosphates, which consequently play a critical role in controlling neutrophil function and would be expected to act as ideal therapeutic targets for enhancing or suppressing innate immune responses. Here, we comprehensively review current understanding about the action of lipid phosphatases and inositol phosphates in the control of neutrophil function in infection and inflammation.
authors.affiliation: Department of Pathology, Harvard Medical School, Boston, MA, USA Department of Lab Medicine, Children's Hospital Boston, Dana-Farber/Harvard Cancer Center, Boston, MA, USA hongbo.luo@childrens.harvard.edu.
authors.forename: Hongbo R
authors.initials: HR
authors.lastname: Luo
authors.affiliation: Department of Pathology, Harvard Medical School, Boston, MA, USA Department of Lab Medicine, Children's Hospital Boston, Dana-Farber/Harvard Cancer Center, Boston, MA, USA Promega Corporation, Madison, WI, USA.
authors.forename: Subhanjan
authors.initials: S
authors.lastname: Mondal
mesh_terms: D000818:Animals; D006801:Humans; D007113:Immunity, Innate / Q000502:physiology; D007295:Inositol Phosphates / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism*; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism
chemical_list: D007295:Inositol Phosphates; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols; C060974:phosphatidylinositol 3,4,5-triphosphate
keywords: PtdIns(3,4,5)P3; innate immunity; inositol phosphate; lipid phosphatase; neutrophils