PMID- 10400704
OWN - NLM
STAT- MEDLINE
DCOM- 19990819
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 29
DP  - 1999 Jul 16
TI  - Priming of human neutrophil respiratory burst by granulocyte/macrophage 
      colony-stimulating factor (GM-CSF) involves partial phosphorylation of p47(phox).
PG  - 20704-8
AB  - Neutrophil superoxide production can be potentiated by prior exposure to 
      "priming" agents such as granulocyte/macrophage colony stimulating factor 
      (GM-CSF). Because the mechanism underlying GM-CSF-dependent priming is not 
      understood, we investigated the effects of GM-CSF on the phosphorylation of the 
      cytosolic NADPH oxidase components p47(phox) and p67(phox). Preincubation of 
      neutrophils with GM-CSF alone increased the phosphorylation of p47(phox) but not 
      that of p67(phox). Addition of formyl-methionyl-leucyl-phenylalanine (fMLP) to 
      GM-CSF-pretreated neutrophils resulted in more intense phosphorylation of 
      p47(phox) than with GM-CSF alone and fMLP alone. GM-CSF-induced p47(phox) 
      phosphorylation was time- and concentration-dependent and ran parallel to the 
      priming effect of GM-CSF on superoxide production. Two-dimensional tryptic 
      peptide mapping of p47(phox) showed that GM-CSF induced phosphorylation of one 
      major peptide. fMLP alone induced phosphorylation of several peptides, an effect 
      enhanced by GM-CSF pretreatment. In contrast to fMLP and phorbol 12-myristate 
      13-acetate, GM-CSF-induced phosphorylation of p47(phox) was not inhibited by the 
      protein kinase C inhibitor GF109203X. The protein-tyrosine kinase inhibitor 
      genistein and the phosphatidylinositol 3-kinase inhibitor wortmannin inhibited 
      the phosphorylation of p47(phox) induced by GM-CSF and by fMLP but not that 
      induced by phorbol 12-myristate 13-acetate. GM-CSF alone did not induce p47(phox) 
      or p67(phox) translocation to the membrane, but neutrophils treated consecutively 
      with GM-CSF and fMLP showed an increase (compared with fMLP alone) in membrane 
      translocation of p47(phox) and p67(phox). Taken together, these results show that 
      the priming action of GM-CSF on the neutrophil respiratory burst involves partial 
      phosphorylation of p47(phox) on specific serines and suggest the involvement of a 
      priming pathway regulated by protein-tyrosine kinase and phosphatidylinositol 
      3-kinase.
FAU - Dang, P M
AU  - Dang PM
AD  - INSERM U. 479, Centre Hospitalier Universitaire Xavier Bichat, Faculte de 
      Medecine, 16 rue Henri Huchard, 75018 Paris, France.
FAU - Dewas, C
AU  - Dewas C
FAU - Gaudry, M
AU  - Gaudry M
FAU - Fay, M
AU  - Fay M
FAU - Pedruzzi, E
AU  - Pedruzzi E
FAU - Gougerot-Pocidalo, M A
AU  - Gougerot-Pocidalo MA
FAU - El Benna, J
AU  - El Benna J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Phosphoproteins)
RN  - 0 (neutrophil cytosol factor 67K)
RN  - 11062-77-4 (Superoxides)
RN  - 59880-97-6 (N-Formylmethionine Leucyl-Phenylalanine)
RN  - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor)
RN  - EC 1.6.3.- (NADPH Oxidases)
RN  - EC 1.6.3.1 (neutrophil cytosolic factor 1)
RN  - EC 2.7.11.13 (Protein Kinase C)
SB  - IM
MH  - Biological Transport
MH  - Enzyme Inhibitors/pharmacology
MH  - Granulocyte-Macrophage Colony-Stimulating Factor/*pharmacology
MH  - Humans
MH  - N-Formylmethionine Leucyl-Phenylalanine/pharmacology
MH  - NADPH Oxidases
MH  - Neutrophils/*drug effects/metabolism
MH  - Phosphoproteins/*metabolism
MH  - Phosphorylation
MH  - Protein Kinase C/antagonists & inhibitors
MH  - Respiratory Burst/*drug effects
MH  - Superoxides/metabolism
EDAT- 1999/07/10 00:00
MHDA- 1999/07/10 00:01
CRDT- 1999/07/10 00:00
PHST- 1999/07/10 00:00 [pubmed]
PHST- 1999/07/10 00:01 [medline]
PHST- 1999/07/10 00:00 [entrez]
AID - S0021-9258(19)72705-7 [pii]
AID - 10.1074/jbc.274.29.20704 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Jul 16;274(29):20704-8. doi: 10.1074/jbc.274.29.20704.