Evidence for IL-12-activated Ca2+ and tyrosine signaling pathways in human neutrophils

J Immunol. 1998 Oct 1;161(7):3737-45.

Abstract

The cytokine IL-12 is proposed to play a bridging role between innate and adaptive immunity. Here we demonstrate that IL-12 binds specifically to human neutrophils. This binding leads to a transient increase in 1) intracellular free calcium due to its release from membrane-enclosed stores and its influx from extracellular medium, 2) actin polymerization, and 3) tyrosine phosphorylation. IL-12 treatment also leads to a concentration-dependent increase in reactive oxygen metabolite production. The effect of IL-12 is blocked by neutralizing Abs to IL-12. Inhibition of either calcium transient or tyrosine phosphorylation causes inhibition of reactive oxygen metabolite production. However, inhibition of actin polymerization enhances IL-12-induced oxidase activation. Our data suggest 1) a direct role for IL-12 in the activation of human neutrophils, and 2) a calcium-dependent signaling pathway for IL-12.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Calcium / metabolism*
  • Calcium / physiology
  • Humans
  • Interleukin-12 / metabolism
  • Interleukin-12 / physiology*
  • Neutrophil Activation / drug effects
  • Neutrophils / drug effects
  • Neutrophils / immunology
  • Neutrophils / metabolism*
  • Phosphorylation / drug effects
  • Polymers / metabolism
  • Protein Binding / immunology
  • Signal Transduction / drug effects
  • Signal Transduction / immunology*
  • Tyrosine / metabolism*
  • Tyrosine / physiology

Substances

  • Actins
  • Polymers
  • Interleukin-12
  • Tyrosine
  • Calcium