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Granulocyte-macrophage colony-stimulating factor primes neutrophils by activating a pertussis toxin-sensitive G protein not associated with phosphatidylinositol turnover.

Publication ,  Journal Article
Corey, SJ; Rosoff, PM
Published in: J Biol Chem
August 25, 1989

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a hematopoietic cytokine which produces diverse biological effects in target cells of myeloid origin. GM-CSF enhances the production of superoxide anion (O2-) by mature neutrophils in response to chemotactic peptides such as formyl-methionyl-leucyl-phenylalanine (fMLP), but alone it has no effect on this system. This process has been termed "priming." fMLP activates neutrophils via a pertussis toxin-sensitive GTP-binding protein, leading to the rapid production of the second messengers diacylglycerol (DAG) and inositol trisphosphate, via phosphatidylinositol turnover, and arachidonic acid (AA) by a presumptive phospholipase A2-mediated mechanism. All three second messengers may lead to the generation of O2-. We investigated the effect of priming of GM-CSF on these systems. GM-CSF had no effect on fMLP-stimulated DAG and inositol trisphosphate levels, nor did it amplify the response to exogenously added phorbol ester (to mimic the action of DAG) or calcium ionophore. Neutrophils primed with the cytokine showed a small, but significant, enhancement of fMLP-stimulated AA release. Compared with unprimed controls, primed neutrophils also showed a significant increase in O2- production when stimulated with either AA or the nonhydrolyzable GTP analogue, GTP-gamma-S. The magnitude of enhanced O2- production was similar to that observed after fMLP treatment of primed cells. All of these effects, including the increased sensitivity to AA treatment, were inhibited by pertussis toxin. These data show that GM-CSF primes neutrophils by modulating the activity of at least one pertussis toxin-sensitive G protein coupled to a metabolic pathway that mobilizes and utilizes arachidonic acid.

Duke Scholars

Published In

J Biol Chem

ISSN

0021-9258

Publication Date

August 25, 1989

Volume

264

Issue

24

Start / End Page

14165 / 14171

Location

United States

Related Subject Headings

  • Virulence Factors, Bordetella
  • Superoxides
  • Recombinant Proteins
  • Protein Kinase C
  • Phosphatidylinositols
  • Pertussis Toxin
  • Neutrophils
  • NADPH Oxidases
  • NADH, NADPH Oxidoreductases
  • Humans
 

Published In

J Biol Chem

ISSN

0021-9258

Publication Date

August 25, 1989

Volume

264

Issue

24

Start / End Page

14165 / 14171

Location

United States

Related Subject Headings

  • Virulence Factors, Bordetella
  • Superoxides
  • Recombinant Proteins
  • Protein Kinase C
  • Phosphatidylinositols
  • Pertussis Toxin
  • Neutrophils
  • NADPH Oxidases
  • NADH, NADPH Oxidoreductases
  • Humans