Dataset Information
Microvascular Mimetics for the Study of Leukocyte-Endothelial Interactions.
Ontology highlight
ABSTRACT: Introduction
The pathophysiological increase in microvascular permeability plays a well-known role in the onset and progression of diseases like sepsis and atherosclerosis. However, how interactions between neutrophils and the endothelium alter vessel permeability is often debated.Methods
In this study, we introduce a microfluidic, silicon-membrane enabled vascular mimetic (?SiM-MVM) for investigating the role of neutrophils in inflammation-associated microvascular permeability. In utilizing optically transparent silicon nanomembrane technology, we build on previous microvascular models by enabling in situ observations of neutrophil-endothelium interactions. To evaluate the effects of neutrophil transmigration on microvascular model permeability, we established and validated electrical (transendothelial electrical resistance and impedance) and small molecule permeability assays that allow for the in situ quantification of temporal changes in endothelium junctional integrity.Results
Analysis of neutrophil-expressed ?1 integrins revealed a prominent role of neutrophil transmigration and basement membrane interactions in increased microvascular permeability. By utilizing blocking antibodies specific to the ?1 subunit, we found that the observed increase in microvascular permeability due to neutrophil transmigration is constrained when neutrophil-basement membrane interactions are blocked. Having demonstrated the value of in situ measurements of small molecule permeability, we then developed and validated a quantitative framework that can be used to interpret barrier permeability for comparisons to conventional Transwell™ values.Conclusions
Overall, our results demonstrate the potential of the ?SiM-MVM in elucidating mechanisms involved in the pathogenesis of inflammatory disease, and provide evidence for a role for neutrophils in inflammation-associated endothelial barrier disruption.
SUBMITTER: Khire TS
PROVIDER: S-EPMC7048879 | biostudies-literature | 2020 Apr
REPOSITORIES: biostudies-literature
Publications
Microvascular Mimetics for the Study of Leukocyte-Endothelial Interactions.
Cellular and molecular bioengineering 20200131 2
<h4>Introduction</h4>The pathophysiological increase in microvascular permeability plays a well-known role in the onset and progression of diseases like sepsis and atherosclerosis. However, how interactions between neutrophils and the endothelium alter vessel permeability is often debated.<h4>Methods</h4>In this study, we introduce a microfluidic, silicon-membrane enabled vascular mimetic (μSiM-MVM) for investigating the role of neutrophils in inflammation-associated microvascular permeability. ...[more]
