Molecular control of PtdIns(3,4,5)P3 signaling in neutrophils

EMBO Rep. 2015 Feb;16(2):149-63. doi: 10.15252/embr.201439466. Epub 2015 Jan 9.

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.

Keywords: PtdIns(3,4,5)P3; innate immunity; inositol phosphate; lipid phosphatase; neutrophils.

Publication types

  • Review

MeSH terms

  • Animals
  • Humans
  • Immunity, Innate / physiology
  • Inositol Phosphates / metabolism
  • Neutrophils / metabolism*
  • Phosphatidylinositol Phosphates / metabolism
  • Phosphatidylinositols / metabolism

Substances

  • Inositol Phosphates
  • Phosphatidylinositol Phosphates
  • Phosphatidylinositols
  • phosphatidylinositol 3,4,5-triphosphate