PMID- 12947016
OWN - NLM
STAT- MEDLINE
DCOM- 20040225
LR  - 20131121
IS  - 1524-4636 (Electronic)
IS  - 1079-5642 (Linking)
VI  - 23
IP  - 10
DP  - 2003 Oct 1
TI  - Mechanisms of leukotriene B4--triggered monocyte adhesion.
PG  - 1761-7
AB  - OBJECTIVE: Leukotriene B4 (LTB4) has been implicated in the trafficking of 
      monocytes to inflammatory pathologic conditions, 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 beta1- and beta2-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.
FAU - Friedrich, Erik B
AU  - Friedrich EB
AD  - Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, 
      Charlestown 02129, USA.
FAU - Tager, Andrew M
AU  - Tager AM
FAU - Liu, Emerson
AU  - Liu E
FAU - Pettersson, Annika
AU  - Pettersson A
FAU - Owman, Christer
AU  - Owman C
FAU - Munn, Lance
AU  - Munn L
FAU - Luster, Andrew D
AU  - Luster AD
FAU - Gerszten, Robert E
AU  - Gerszten RE
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20030828
PL  - United States
TA  - Arterioscler Thromb Vasc Biol
JT  - Arteriosclerosis, thrombosis, and vascular biology
JID - 9505803
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chemotactic Factors)
RN  - 0 (Receptors, Leukotriene B4)
RN  - 1HGW4DR56D (Leukotriene B4)
SB  - IM
MH  - Animals
MH  - Cell Adhesion/drug effects/physiology
MH  - Cells, Cultured
MH  - Chemokine CCL2/physiology
MH  - Chemotactic Factors/pharmacology
MH  - Endothelium, Vascular
MH  - Flow Cytometry
MH  - Humans
MH  - Leukotriene B4/*physiology
MH  - Mesenteric Arteries
MH  - Monocytes/chemistry/*physiology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Leukotriene B4/analysis/antagonists & inhibitors/*physiology
MH  - Signal Transduction
EDAT- 2003/08/30 05:00
MHDA- 2004/02/26 05:00
CRDT- 2003/08/30 05:00
PHST- 2003/08/30 05:00 [pubmed]
PHST- 2004/02/26 05:00 [medline]
PHST- 2003/08/30 05:00 [entrez]
AID - 01.ATV.0000092941.77774.3C [pii]
AID - 10.1161/01.ATV.0000092941.77774.3C [doi]
PST - ppublish
SO  - Arterioscler Thromb Vasc Biol. 2003 Oct 1;23(10):1761-7. doi: 
      10.1161/01.ATV.0000092941.77774.3C. Epub 2003 Aug 28.