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Leukotriene B4-Neutrophil Elastase Axis Drives Neutrophil Reverse Transendothelial Cell Migration In Vivo

Colom, Bartomeu
Bodkin, Jennifer V
Beyrau, Martina
Woodfin, Abigail
Rourke, Claire
Chavakis, Triantafyllos
Brohi, Karim
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Published in Immunity. 2015, vol. 42, no. 6, p. 1075-86
Abstract Breaching endothelial cells (ECs) is a decisive step in the migration of leukocytes from the vascular lumen to the extravascular tissue, but fundamental aspects of this response remain largely unknown. We have previously shown that neutrophils can exhibit abluminal-to-luminal migration through EC junctions within mouse cremasteric venules and that this response is elicited following reduced expression and/or functionality of the EC junctional adhesion molecule-C (JAM-C). Here we demonstrate that the lipid chemoattractant leukotriene B4 (LTB4) was efficacious at causing loss of venular JAM-C and promoting neutrophil reverse transendothelial cell migration (rTEM) in vivo. Local proteolytic cleavage of EC JAM-C by neutrophil elastase (NE) drove this cascade of events as supported by presentation of NE to JAM-C via the neutrophil adhesion molecule Mac-1. The results identify local LTB4-NE axis as a promoter of neutrophil rTEM and provide evidence that this pathway can propagate a local sterile inflammatory response to become systemic.
Keywords AnimalsBenzoates/administration & dosageCell Adhesion Molecules/genetics/metabolismCells, CulturedEndothelial Cells/physiologyHumansImmunoglobulins/genetics/metabolismIntercellular Junctions/drug effectsLeukocyte Elastase/genetics/metabolismLeukotriene B4/administration & dosage/metabolismMacrophage-1 Antigen/metabolismMiceMice, Inbred C57BLMice, KnockoutNeutrophils/immunologyReperfusion Injury/immunologyTransendothelial and Transepithelial Migration/drug effects/immunologyVenules/physiologyWounds and Injuries/immunology
PMID: 26047922
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Research group Molécules d'adhésion et processus de migration cellulaire (167)
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COLOM, Bartomeu et al. Leukotriene B4-Neutrophil Elastase Axis Drives Neutrophil Reverse Transendothelial Cell Migration In Vivo. In: Immunity, 2015, vol. 42, n° 6, p. 1075-86. doi: 10.1016/j.immuni.2015.05.010 https://archive-ouverte.unige.ch/unige:83915

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Deposited on : 2016-05-27

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