PMID- 2547784
OWN - NLM
STAT- MEDLINE
DCOM- 19890913
LR  - 20210210
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 264
IP  - 24
DP  - 1989 Aug 25
TI  - Granulocyte-macrophage colony-stimulating factor primes neutrophils by activating 
      a pertussis toxin-sensitive G protein not associated with phosphatidylinositol 
      turnover.
PG  - 14165-71
AB  - 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.
FAU - Corey, S J
AU  - Corey SJ
AD  - Division of Hematology-Oncology, Harvard Medical School, Boston, Massachusetts.
FAU - Rosoff, P M
AU  - Rosoff PM
LA  - eng
GR  - 2T32CA09172-12/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Arachidonic Acids)
RN  - 0 (Colony-Stimulating Factors)
RN  - 0 (Growth Substances)
RN  - 0 (Phosphatidylinositols)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Virulence Factors, Bordetella)
RN  - 11062-77-4 (Superoxides)
RN  - 27YG812J1I (Arachidonic Acid)
RN  - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor)
RN  - EC 1.6.- (NADH, NADPH Oxidoreductases)
RN  - EC 1.6.3.- (NADPH Oxidases)
RN  - EC 2.4.2.31 (Pertussis Toxin)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - EC 3.6.1.- (GTP-Binding Proteins)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Adult
MH  - Arachidonic Acid
MH  - Arachidonic Acids/metabolism
MH  - Binding, Competitive
MH  - Calcium/physiology
MH  - Colony-Stimulating Factors/*pharmacology
MH  - GTP-Binding Proteins/biosynthesis/*physiology
MH  - Granulocyte-Macrophage Colony-Stimulating Factor
MH  - Growth Substances/*pharmacology
MH  - Humans
MH  - NADH, NADPH Oxidoreductases/metabolism
MH  - NADPH Oxidases
MH  - Neutrophils/metabolism/*physiology
MH  - *Pertussis Toxin
MH  - Phosphatidylinositols/*metabolism
MH  - Protein Kinase C/pharmacology
MH  - Recombinant Proteins/pharmacology
MH  - Superoxides/biosynthesis
MH  - *Virulence Factors, Bordetella
EDAT- 1989/08/25 00:00
MHDA- 1989/08/25 00:01
CRDT- 1989/08/25 00:00
PHST- 1989/08/25 00:00 [pubmed]
PHST- 1989/08/25 00:01 [medline]
PHST- 1989/08/25 00:00 [entrez]
AID - S0021-9258(18)71657-8 [pii]
PST - ppublish
SO  - J Biol Chem. 1989 Aug 25;264(24):14165-71.