PMID- 14592823
OWN - NLM
STAT- MEDLINE
DCOM- 20040420
LR  - 20210206
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 103
IP  - 5
DP  - 2004 Mar 1
TI  - Platelet factor 4 (PF-4)-induced neutrophil adhesion is controlled by 
      src-kinases, whereas PF-4-mediated exocytosis requires the additional activation 
      of p38 MAP kinase and phosphatidylinositol 3-kinase.
PG  - 1602-10
AB  - Among the various chemokines that are functionally active on neutrophils, 
      platelet factor 4 (PF-4; CXCL4) appears to have a specialized role. Lacking 
      typical chemokine activities, PF-4 stimulates neutrophils to undergo firm 
      adhesion to endothelial cells and, in the presence of an appropriate costimulus 
      like tumor necrosis factor (TNF), PF-4 induces exocytosis of secondary granule 
      contents. Analyzing the individual contribution of PF-4 and its costimuli in the 
      control of these functions at the signaling level, we demonstrate that 
      TNF-induced activation of p38 mitogen-activated protein (MAP) kinase (but not 
      extracellular regulated kinase [Erk] kinases) acts as general and essential 
      costimulatory signal in PF-4-dependent neutrophil exocytosis. This was shown by 
      the use of a specific inhibitor (SB203580), by biologic (lipopolysaccharide, 
      N-formyl-methionyl-leucyl-phenylalanine) and pharmacologic (anisomycin) 
      activators of p38 MAP kinase, and by phosphorylation studies. Furthermore, 
      TNF-mediated activation of phosphatidylinositol 3-kinase (PI 3-kinase) represents 
      an additional essential signaling component in this process as demonstrated by 
      studies with its inhibitor wortmannin as well as by analysis of the 
      phosphorylation of AKT kinase. PF-4, however, directly activates src-kinases and 
      PF-4-induced adherence as well as PF-4/TNF-mediated exocytosis was inhibited by 
      an src-kinase inhibitor PP1. Taken together, neutrophil exocytosis and adherence 
      are regulated on p38 MAP kinase, PI 3-kinase, and src-kinase activation.
FAU - Kasper, Brigitte
AU  - Kasper B
AD  - Department of Immunology and Cell Biology, Research Center Borstel, Borstel, 
      Germany.
FAU - Brandt, Ernst
AU  - Brandt E
FAU - Bulfone-Paus, Silvia
AU  - Bulfone-Paus S
FAU - Petersen, Frank
AU  - Petersen F
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20031030
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Imidazoles)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Pyridines)
RN  - 37270-94-3 (Platelet Factor 4)
RN  - 6C74YM2NGI (Anisomycin)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.10.2 (src-Family Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - EC 3.4.21.- (Lactoferrin)
RN  - OU13V1EYWQ (SB 203580)
SB  - IM
MH  - Anisomycin/pharmacology
MH  - Blotting, Western
MH  - Cell Adhesion
MH  - Cells, Cultured
MH  - Enzyme Activation
MH  - Enzyme Inhibitors/pharmacology
MH  - Exocytosis
MH  - Humans
MH  - Imidazoles/pharmacology
MH  - Lactoferrin/metabolism
MH  - Lipopolysaccharides/chemistry
MH  - Mitogen-Activated Protein Kinases/*metabolism
MH  - Neutrophils/*cytology/metabolism
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - Phosphorylation
MH  - Platelet Factor 4/metabolism/*physiology
MH  - Precipitin Tests
MH  - Pyridines/pharmacology
MH  - Signal Transduction
MH  - Time Factors
MH  - p38 Mitogen-Activated Protein Kinases
MH  - src-Family Kinases/*metabolism
EDAT- 2003/11/01 05:00
MHDA- 2004/04/21 05:00
CRDT- 2003/11/01 05:00
PHST- 2003/11/01 05:00 [pubmed]
PHST- 2004/04/21 05:00 [medline]
PHST- 2003/11/01 05:00 [entrez]
AID - S0006-4971(20)50067-0 [pii]
AID - 10.1182/blood-2003-08-2802 [doi]
PST - ppublish
SO  - Blood. 2004 Mar 1;103(5):1602-10. doi: 10.1182/blood-2003-08-2802. Epub 2003 Oct 
      30.