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Real-time Imaging of Leukotriene B4 Mediated Cell Migration and BLT1 Interactions with β-arrestin
Published on: December 23, 2010
Leukotriene D4 activates {beta}2-integrin adhesion in human polymorphonuclear leukocytes.
A Y Meliton1, N M Muñoz, C M Osan
1Dept of Medicine, M6076, The University of Chicago, 5841 S. Maryland Avenue, Chicago, IL 60637, USA.
The European Respiratory Journal
|August 15, 2009
Summary
Leukotriene D4 activates the cysteinyl leukotriene-1 receptor (cysLT(1)R) on neutrophils, increasing beta(2)-integrin adhesion to ICAM-1. This process involves group IVa phospholipase A2 (gIVaPLA2) phosphorylation.
Area of Science:
- Immunology
- Cell Biology
- Pharmacology
Background:
- Cysteinyl leukotriene-1 receptor (cysLT(1)R) plays a role in inflammatory responses.
- Beta(2)-integrin adhesion to ICAM-1 is crucial for leukocyte migration.
Purpose of the Study:
- To investigate the role of cysLT(1)R activation in regulating beta(2)-integrin adhesion to ICAM-1 in human polymorphonuclear leukocytes (PMNs).
- To elucidate the underlying mechanisms of this regulation.
Main Methods:
- Isolation of human peripheral blood PMNs and eosinophils.
- Immunofluorescence and Western blot analysis for cysLT(1)R expression.
- Leukotriene D4 (LTD4) stimulation assays to measure beta(2)-integrin adhesion.
- Assessment of gIVaPLA2 phosphorylation.
- Inhibition studies using montelukast (cysLT(1)R antagonist) and trifluoromethylketone (gIVaPLA2 inhibitor).
Main Results:
- LTD4 upregulated beta(2)-integrin adhesion of PMNs to ICAM-1 in a time- and concentration-dependent manner.
- This upregulation was temporally and quantitatively linked to the phosphorylation of 85-kDa cytosolic group IVa phospholipase A2 (gIVaPLA2).
- Montelukast and gIVaPLA2 inhibition blocked LTD4-induced adhesion.
Conclusions:
- LTD4-induced upregulation of beta(2)-integrin adhesion to ICAM-1 in PMNs is mediated by cysLT(1)R activation.
- Phosphorylation of gIVaPLA2 is a critical step in this pathway.
- These findings highlight a key mechanism in inflammatory cell adhesion.
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