Transendothelial migration enables subsequent transmigration of neutrophils through underlying pericytes

During acute inflammation, neutrophil recruitment into extravascular tissue requires neutrophil tethering and rolling on cytokine-activated endothelial cells (ECs), tight adhesion, crawling towards EC junctions and transendothelial migration (TEM). Following TEM, neutrophils must still traverse the...

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Bibliographic Details
Published in:PloS one 2013-03, Vol.8 (3), p.e60025
Main Authors: Ayres-Sander, Chantal E, Lauridsen, Holly, Maier, Cheryl L, Sava, Parid, Pober, Jordan S, Gonzalez, Anjelica L
Format: Article
Language:English
Subjects:
Adhesion
Biology
Biomedical engineering
CD18 Antigens - metabolism
CD18 Antigens - pharmacology
Cell adhesion & migration
Cell Adhesion - drug effects
Cell Movement - drug effects
Cell Polarity - drug effects
Cells, Cultured
Chemokines
Cytokines
Endothelial cells
Engineering
Humans
Inflammation
Intercellular adhesion molecule 1
Intercellular Adhesion Molecule-1 - metabolism
Interleukin 8
Interleukin-8 - metabolism
Leukocyte migration
Leukocytes (neutrophilic)
Mac1 protein
Medicine
Microvasculature
Monolayers
Neutrophils
Neutrophils - cytology
Neutrophils - drug effects
Neutrophils - metabolism
Pericytes
Pericytes - cytology
Permeability
Tethering
Transendothelial and Transepithelial Migration - drug effects
Veins & arteries
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Summary:During acute inflammation, neutrophil recruitment into extravascular tissue requires neutrophil tethering and rolling on cytokine-activated endothelial cells (ECs), tight adhesion, crawling towards EC junctions and transendothelial migration (TEM). Following TEM, neutrophils must still traverse the subendothelial basement membrane and network of pericytes (PCs). Until recently, the contribution of the PC layer to neutrophil recruitment was largely ignored. Here we analyze human neutrophil interactions with interleukin (IL)-1β-activated human EC monolayers, PC monolayers and EC/PC bilayers in vitro. Compared to EC, PC support much lower levels of neutrophil binding (54.6% vs. 7.1%, respectively) and transmigration (63.7 vs. 8.8%, respectively) despite comparable levels of IL-8 (CXCL8) synthesis and display. Remarkably, EC/PC bilayers support intermediate levels of transmigration (37.7%). Neutrophil adhesion to both cell types is Mac-1-dependent and while ICAM-1 transduction of PCs increases neutrophil adhesion to (41.4%), it does not increase transmigration through PC monolayers. TEM, which increases neutrophil Mac-1 surface expression, concomitantly increases the ability of neutrophils to traverse PCs (19.2%). These data indicate that contributions from both PCs and ECs must be considered in evaluation of microvasculature function in acute inflammation.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0060025