Premium
Human Microvascular Pericyte Basement Membrane Remodeling Regulates Neutrophil Recruitment
Author(s) -
Sava Parid,
Cook Ian O.,
Mahal Rajwant S.,
Gonzalez Anjelica L.
Publication year - 2015
Publication title -
microcirculation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.793
H-Index - 83
eISSN - 1549-8719
pISSN - 1073-9688
DOI - 10.1111/micc.12173
Subject(s) - fibronectin , pericyte , microbiology and biotechnology , chemistry , extracellular matrix , cell adhesion molecule , basement membrane , inflammation , cell adhesion , immunology , biology , endothelial stem cell , cell , in vitro , biochemistry
Abstract Objective Neutrophil extravasation at post‐capillary venules, consisting of EC , PC, and the shared ECM , increases following fibrotic remodeling in the lung, liver, and skin. The role of fibrotic pericyte‐derived ECM in regulating EC activation and neutrophil recruitment remains unexplored. Methods To elucidate the role of human pericyte‐derived ECM in EC activation, we characterized PC ‐derived ECM following transforming growth factor‐ β 1, IL‐1 β , CCL2, or bleomycin activation, and examined surface adhesion molecule expression and neutrophil recruitment by EC cultured on PC ‐ ECM . Results Pro‐inflammatory activation of PC‐induced deposition of compositionally distinct ECM compared with non‐activated control. Bleomycin activation induced fibronectin‐rich and collagen‐poor ECM remodeling by PC, facilitating increased neutrophil transendothelial migration when compared with non‐activated pericyte ECM (49.9 ± 3.4% versus 29.7 ± 1.4%). Increases in fibronectin compared to collagen I, are largely responsible for ECM ‐regulated neutrophil recruitment, as EC cultured on fibronectin supported increased neutrophil transmigration compared to collagen I (51.6 ± 6.2% versus 28.0 ± 4.8%). We attribute this difference to increased expression of ICAM‐1 and its redistribution to EC borders. Conclusions This is the first demonstration of human pericyte sensitivity to inflammatory stimuli, inducing fibrotic matrix deposition that regulates EC adhesion molecule expression and neutrophil recruitment.