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Mechanisms of leukotriene B-4-triggered monocyte adhesion

Friedrich, EB; Tager, AM; Liu, E; Pettersson, Annika LU ; Owman, Christer LU ; Munn, L; Luster, AD and Gerszten, RE (2003) In Arteriosclerosis, Thrombosis and Vascular Biology 23(10). p.1761-1767
Abstract
Objective - Leukotriene B-4 (LTB4) has been implicated in the trafficking of monocytes to inflammatory pathologicconditions, such as transplant rejection and atherosclerosis. The aim of this study was to determine the mechanisms by which LTB4 contributes to monocyte capture from the circulation. Methods and Results - In in vitro and in vivo vascular models, the lipid chemoattractant LTB4 was an equipotent agonist of monocyte adhesion compared with the chemokine monocyte chemoattractant protein-1 (MCP-1). Adenoviral gene transfer of specific endothelial adhesion molecules and blocking monoclonal antibody studies demonstrated that LTB4 triggers both beta(1)- and beta(2)-integrin-dependent adhesion. Flow cytometry studies suggested that... (More)
Objective - Leukotriene B-4 (LTB4) has been implicated in the trafficking of monocytes to inflammatory pathologicconditions, such as transplant rejection and atherosclerosis. The aim of this study was to determine the mechanisms by which LTB4 contributes to monocyte capture from the circulation. Methods and Results - In in vitro and in vivo vascular models, the lipid chemoattractant LTB4 was an equipotent agonist of monocyte adhesion compared with the chemokine monocyte chemoattractant protein-1 (MCP-1). Adenoviral gene transfer of specific endothelial adhesion molecules and blocking monoclonal antibody studies demonstrated that LTB4 triggers both beta(1)- and beta(2)-integrin-dependent adhesion. Flow cytometry studies suggested that changes in integrin avidity or affinity, rather than alterations of integrin surface expression, were responsible for the chemoattractant-triggered arrest. Surprisingly, in contrast to the peptide chemokine MCP-1, LTB4 did not activate the phosphoinositide 3-kinase pathway, which is a functionally critical step in chemokine-triggered effector functions. Conclusions - LTB4 is a potent trigger of monocyte adhesion under flow yet mediates its effects via pathways that appear to differ from peptide chemoattractants. A better understanding of the mechanisms of LTB4-induced monocyte trafficking might shed insight into disease pathogenesis and pinpoint critical steps for therapeutic intervention for multiple human inflammatory pathologic conditions. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Arteriosclerosis, Thrombosis and Vascular Biology
volume
23
issue
10
pages
1761 - 1767
publisher
American Heart Association
external identifiers
  • pmid:12947016
  • wos:000185850200013
  • scopus:0141988910
ISSN
1524-4636
DOI
language
English
LU publication?
yes
id
4b76ec28-afc5-469b-ac51-3dd23eeebca6 (old id 298526)
date added to LUP
2007-09-03 09:18:01
date last changed
2018-05-29 11:57:28
@article{4b76ec28-afc5-469b-ac51-3dd23eeebca6,
  abstract     = {Objective - Leukotriene B-4 (LTB4) has been implicated in the trafficking of monocytes to inflammatory pathologicconditions, such as transplant rejection and atherosclerosis. The aim of this study was to determine the mechanisms by which LTB4 contributes to monocyte capture from the circulation. Methods and Results - In in vitro and in vivo vascular models, the lipid chemoattractant LTB4 was an equipotent agonist of monocyte adhesion compared with the chemokine monocyte chemoattractant protein-1 (MCP-1). Adenoviral gene transfer of specific endothelial adhesion molecules and blocking monoclonal antibody studies demonstrated that LTB4 triggers both beta(1)- and beta(2)-integrin-dependent adhesion. Flow cytometry studies suggested that changes in integrin avidity or affinity, rather than alterations of integrin surface expression, were responsible for the chemoattractant-triggered arrest. Surprisingly, in contrast to the peptide chemokine MCP-1, LTB4 did not activate the phosphoinositide 3-kinase pathway, which is a functionally critical step in chemokine-triggered effector functions. Conclusions - LTB4 is a potent trigger of monocyte adhesion under flow yet mediates its effects via pathways that appear to differ from peptide chemoattractants. A better understanding of the mechanisms of LTB4-induced monocyte trafficking might shed insight into disease pathogenesis and pinpoint critical steps for therapeutic intervention for multiple human inflammatory pathologic conditions.},
  author       = {Friedrich, EB and Tager, AM and Liu, E and Pettersson, Annika and Owman, Christer and Munn, L and Luster, AD and Gerszten, RE},
  issn         = {1524-4636},
  language     = {eng},
  number       = {10},
  pages        = {1761--1767},
  publisher    = {American Heart Association},
  series       = {Arteriosclerosis, Thrombosis and Vascular Biology},
  title        = {Mechanisms of leukotriene B-4-triggered monocyte adhesion},
  url          = {http://dx.doi.org/},
  volume       = {23},
  year         = {2003},
}