Leukotriene B4-Neutrophil Elastase Axis Drives Neutrophil Reverse Transendothelial Cell Migration InVivo
Research output: Contribution to journal › Research article › Contributed › peer-review
Contributors
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) invivo. 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.
Details
Original language | English |
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Pages (from-to) | 1075-1086 |
Number of pages | 12 |
Journal | Immunity |
Volume | 42 |
Issue number | 6 |
Publication status | Published - 16 Jun 2015 |
Peer-reviewed | Yes |
External IDs
researchoutputwizard | legacy.publication#66863 |
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Scopus | 84937634493 |
PubMed | 26047922 |