PMID- 12842851
OWN - NLM
STAT- MEDLINE
DCOM- 20040330
LR  - 20180815
IS  - 1044-1549 (Print)
IS  - 1044-1549 (Linking)
VI  - 30
IP  - 3
DP  - 2004 Mar
TI  - Activation of extracellular regulated kinases is required for the increase in 
      airway epithelial permeability during leukocyte transmigration.
PG  - 261-70
AB  - The goal of this study was to determine whether the extracellular regulated 
      kinases (ERK1/2) are involved in leukocyte transmigration across airway 
      epithelium and the associated changes in epithelial permeability. In vitro, we 
      used formyl-methionyl-leucyl-phenylalanine (fMLP) to induce migration of HL-60 
      cells (a human leukocyte cell line) across sheets of polarized Calu-3 airway 
      epithelial cells and also to induce migration of human neutrophils across primary 
      cultures of cow tracheal epithelial cells. In both systems, leukocyte migration 
      decreased transepithelial electrical resistance (R(te)), increased epithelial 
      permeability to albumin (P(alb)), and increased ERK1/2 phosphorylation in 
      epithelial cells. Leukocyte migration and the associated changes in R(te), 
      P(alb), and ERK1/2 phosphorylation were inhibited by calphostin C, a blocker of 
      protein kinase C (PKC), and by PD98059 (a blocker of ERK1/2). Leukocyte 
      transmigration in rat tracheas in vivo was induced with fMLP, and was associated 
      with increased P(alb) and phosphorylation of epithelial ERK1/2. Again, migration 
      and the associated changes were inhibited by luminal PD98059 or calphostin C 
      though neither agent affected rat leukocyte migration in Boyden chambers in 
      vitro. We conclude that PKC and ERK1/2 pathways are activated in airway 
      epithelial cells during migration of leukocytes and are important regulators of 
      airway epithelial permeability.
FAU - Serikov, Vladimir B
AU  - Serikov VB
AD  - Children's Hospital Oakland Research Institute, California, USA.
FAU - Choi, Hyon
AU  - Choi H
FAU - Chmiel, Ken J
AU  - Chmiel KJ
FAU - Wu, Reen
AU  - Wu R
FAU - Widdicombe, Jonathan H
AU  - Widdicombe JH
LA  - eng
GR  - AI50496/AI/NIAID NIH HHS/United States
GR  - HL60288/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20030703
PL  - United States
TA  - Am J Respir Cell Mol Biol
JT  - American journal of respiratory cell and molecular biology
JID - 8917225
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Flavonoids)
RN  - 0 (Naphthalenes)
RN  - 59880-97-6 (N-Formylmethionine Leucyl-Phenylalanine)
RN  - EC 2.7.11.13 (Protein Kinase C)
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  - I271P23G24 (calphostin C)
RN  - SJE1IO5E3I (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one)
SB  - IM
MH  - Animals
MH  - Cattle
MH  - Cell Movement/physiology
MH  - Enzyme Activation/drug effects
MH  - Enzyme Inhibitors/pharmacology
MH  - Flavonoids/pharmacology
MH  - HL-60 Cells
MH  - Humans
MH  - Leukocytes/*physiology
MH  - Male
MH  - Mitogen-Activated Protein Kinase 1/antagonists & inhibitors/*metabolism
MH  - Mitogen-Activated Protein Kinase 3
MH  - Mitogen-Activated Protein Kinases/antagonists & inhibitors/*metabolism
MH  - N-Formylmethionine Leucyl-Phenylalanine/pharmacology
MH  - Naphthalenes/pharmacology
MH  - Neutrophils/cytology/metabolism
MH  - Permeability
MH  - Phosphorylation
MH  - Protein Kinase C/antagonists & inhibitors
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Respiratory Mucosa/*metabolism
MH  - Trachea/cytology/metabolism
EDAT- 2003/07/05 05:00
MHDA- 2004/03/31 05:00
CRDT- 2003/07/05 05:00
PHST- 2003/07/05 05:00 [pubmed]
PHST- 2004/03/31 05:00 [medline]
PHST- 2003/07/05 05:00 [entrez]
AID - 2003-0053OC [pii]
AID - 10.1165/rcmb.2003-0053OC [doi]
PST - ppublish
SO  - Am J Respir Cell Mol Biol. 2004 Mar;30(3):261-70. doi: 10.1165/rcmb.2003-0053OC. 
      Epub 2003 Jul 3.