title: Transendothelial migration enables subsequent transmigration of neutrophils through underlying pericytes.
abstract: 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.
authors.affiliation: Department of Biomedical Engineering, Yale University, New Haven, CT, USA.
authors.forename: Chantal E
authors.initials: CE
authors.lastname: Ayres-Sander
authors.forename: Holly
authors.initials: H
authors.lastname: Lauridsen
authors.forename: Cheryl L
authors.initials: CL
authors.lastname: Maier
authors.forename: Parid
authors.initials: P
authors.lastname: Sava
authors.forename: Jordan S
authors.initials: JS
authors.lastname: Pober
authors.forename: Anjelica L
authors.initials: AL
authors.lastname: Gonzalez
mesh_terms: D018821:CD18 Antigens / Q000378:metabolism / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D016764:Cell Polarity / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D009504:Neutrophils / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D020286:Pericytes / Q000166:cytology*; D057705:Transendothelial and Transepithelial Migration / Q000187:drug effects*
chemical_list: D018821:CD18 Antigens; D016209:Interleukin-8; D018799:Intercellular Adhesion Molecule-1
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