PMID- 11292734
OWN - NLM
STAT- MEDLINE
DCOM- 20010510
LR  - 20181113
IS  - 0019-9567 (Print)
IS  - 1098-5522 (Electronic)
IS  - 0019-9567 (Linking)
VI  - 69
IP  - 5
DP  - 2001 May
TI  - Activation of extracellular signal-related protein kinases 1 and 2 of the 
      mitogen-activated protein kinase family by lipopolysaccharide requires plasma in 
      neutrophils from adults and newborns.
PG  - 3143-9
AB  - Neutrophils exposed to low concentrations of gram-negative lipopolysaccharide 
      (LPS) become primed and have an increased oxidative response to a second stimulus 
      (e.g., formyl-methionyl-leucyl-phenylalanine [fMLP]). In studies aimed at 
      understanding newborn sepsis, we have shown that neutrophils of newborns are not 
      primed in response to LPS. To further understand the processes involved in 
      LPS-mediated priming of neutrophils, we explored the role of extracellular 
      signal-related protein kinases (ERK 1 and 2) of the mitogen-activated protein 
      kinase family. We found that LPS activated ERK 1 and 2 in cells of both adults 
      and newborns and that activation was plasma dependent (maximal at > or =5%) 
      through LPS-binding protein. Although fibronectin in plasma is required for 
      LPS-mediated priming of neutrophils of adults assessed by fMLP-triggered 
      oxidative burst, it was not required for LPS-mediated activation of ERK 1 and 2. 
      LPS-mediated activation was dose and time dependent; maximal activation occurred 
      with approximately 5 ng of LPS per ml and at 10 to 40 min. We used the inhibitor 
      PD 98059 to study the role of ERK 1 and 2 in the LPS-primed fMLP-triggered 
      oxidative burst. While Western blotting showed that 100 microM PD 98059 
      completely inhibited LPS-mediated ERK activation, oxidative response to fMLP by a 
      chemiluminescence assay revealed that the same concentration inhibited the 
      LPS-primed oxidative burst by only 40%. We conclude that in neutrophils, 
      LPS-mediated activation of ERK 1 and 2 requires plasma and that this activation 
      is not dependent on fibronectin. In addition, we found that the ERK pathway is 
      not responsible for the lack of LPS priming in neutrophils of newborns but may be 
      required for 40% of the LPS-primed fMLP-triggered oxidative burst in cells of 
      adults.
FAU - Bonner, S
AU  - Bonner S
AD  - Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia, Canada.
FAU - Yan, S R
AU  - Yan SR
FAU - Byers, D M
AU  - Byers DM
FAU - Bortolussi, R
AU  - Bortolussi R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Infect Immun
JT  - Infection and immunity
JID - 0246127
RN  - 0 (Acute-Phase Proteins)
RN  - 0 (Carrier Proteins)
RN  - 0 (Fibronectins)
RN  - 0 (Flavonoids)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (lipopolysaccharide-binding protein)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - SJE1IO5E3I (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one)
SB  - IM
MH  - *Acute-Phase Proteins
MH  - Adult
MH  - Carrier Proteins/physiology
MH  - Dose-Response Relationship, Drug
MH  - Enzyme Activation/drug effects
MH  - Fibronectins/physiology
MH  - Flavonoids/pharmacology
MH  - Humans
MH  - Infant, Newborn
MH  - Lipopolysaccharides/*pharmacology
MH  - *Membrane Glycoproteins
MH  - Mitogen-Activated Protein Kinase 1/*metabolism
MH  - Mitogen-Activated Protein Kinase 3
MH  - Mitogen-Activated Protein Kinases/*metabolism
MH  - Neutrophils/*enzymology
MH  - Respiratory Burst/drug effects
MH  - Time Factors
PMC - PMC98270
EDAT- 2001/04/09 10:00
MHDA- 2001/05/22 10:01
PMCR- 2001/05/01
CRDT- 2001/04/09 10:00
PHST- 2001/04/09 10:00 [pubmed]
PHST- 2001/05/22 10:01 [medline]
PHST- 2001/04/09 10:00 [entrez]
PHST- 2001/05/01 00:00 [pmc-release]
AID - 1470 [pii]
AID - 10.1128/IAI.69.5.3143-3149.2001 [doi]
PST - ppublish
SO  - Infect Immun. 2001 May;69(5):3143-9. doi: 10.1128/IAI.69.5.3143-3149.2001.