Vascular mimetics based on microfluidics for imaging the leukocyte–endothelial inflammatory response

Schaff, Ulrich Y.; Xing, Malcolm; Lin, Kathleen; Pan, Ning; Jeon, Noo Li; Simon, Scott I.

doi:10.1039/b617915k

Cited by 122 publications

(124 citation statements)

References 31 publications

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“…Vascular mimetic microfluidic flow chambers were employed in order to apply shear stress to murine neutrophils on a substrate of murine L cells transfected with E-selectin and ICAM-1 as described [49,63]. Detailed methods describing how neutrophil arrest was imaged and quantified are included in the Supporting Information.…”

Section: Flow Chambermentioning

confidence: 99%

SLIC‐1/sorting nexin 20: A novel sorting nexin that directs subcellular distribution of PSGL‐1

Schaff¹,

Shih²,

Lorenz³

et al. 2008

Eur J Immunol

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P-Selectin glycoprotein ligand-1 (PSGL-1) is a mucin-like glycoprotein expressed on the surface of leukocytes that serves as the major ligand for the selectin family of adhesion molecules and functions in leukocyte tethering and rolling on activated endothelium and platelets. Previous studies have implicated the highly conserved cytoplasmic domain of PSGL-1 in regulating outside-in signaling of integrin activation. However, molecules that physically and functionally interact with this domain are not completely defined. Using a yeast two-hybrid screen with the cytoplasmic domain of PSGL-1 as bait, a novel protein designated selectin ligand interactor cytoplasmic-1 (SLIC-1) was isolated. Computer-based homology search revealed that SLIC-1 was the human orthologue for the previously identified mouse sorting nexin 20. Direct interaction between SLIC-1 and PSGL-1 was specific as indicated by co-immunoprecipitation and motif mapping. Colocalization experiments demonstrated that SLIC-1 contains a Phox homology domain that binds phosphoinositides and targets the PSGL-1/SLIC-1 complex to endosomes. Deficiency in the murine homologue of SLIC-1 did not modulate PSGL-1-dependent signaling nor alter neutrophil adhesion through PSGL-1. We conclude that SLIC-1 serves as a sorting molecule that cycles PSGL-1 into endosomes with no impact on leukocyte recruitment.Supporting Information for this article is available at http://www.wiley-vch.de/contents/jc_2040/2008/37777_s.pdf IntroductionThe initial tethering and rolling of leukocytes on activated endothelium and platelets is a key biological event mediated by P-selectin glycoprotein ligand-1 (PSGL-1), a mucin-like glycoprotein that functions as a unique high-affinity ligand for the selectin family of adhesion molecules (for reviews, see [1][2][3][4]). Structurally, PSGL-1 is a type I integral membrane protein consisting of an N-terminal selectin-binding domain followed by a region of multiple decameric repeats bearing O-linked glycans, a short transmembrane domain, and lastly a cytoplasmic tail [5][6][7][8][9][10]. Comparison of human and murine PSGL-1 reveals that the 69-amino acid intracellular domain of PSGL-1 is highly conserved. While overall identity between human and Abbreviations: EEA-1: early endosomal antigen-1 Á EGFP: enhanced green fluorescent protein Á ERM: ezrin/radixin/ moesin Á L-E/I: L cell monolayer expressing E-selectin and ICAM-1 Á PI: phosphatidylinositol Á PI 3-kinase: phosphatidylinositol 3-kinase Á PSGL-1: P-selectin glycoprotein ligand-1 Á PtdIns(3)P: phosphatidylinositol 3-phosphate Á PtdIns(3,4)P 2 : phosphatidylinositol 3,4-bisphosphate Á PtdIns(3,4,5)P 3 : phosphatidylinositol 3,4,5-trisphosphate Á PX domain: phox homology domain Á SLIC-1: selectin ligand interactor cytoplasmic-1 Á SNX20: sorting nexin 20 Á TM: transmembrane Ulrich Y. Schaff et al.

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Section: Flow Chambermentioning

confidence: 99%

SLIC‐1/sorting nexin 20: A novel sorting nexin that directs subcellular distribution of PSGL‐1

Schaff¹,

Shih²,

Lorenz³

et al. 2008

Eur J Immunol

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“…These models have been used to study the interactions between the endothelium and other cells, such as leukocytes or cancer cells. [30][31][32][33][34][35][36] However, most current microfluidic blood vessel models only provide a controlled environment for adhesion of individual cancer cells to the endothelium under stimuli. Limited information is available regarding the interaction of tumor aggregates and endothelium, as well as the subsequent events (such as transendothelial invasion or proliferation in situ) that follow adhesion.…”

Section: Introductionmentioning

confidence: 99%

A microfluidic-based device for study of transendothelial invasion of tumor aggregates in realtime

2012

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Circulating tumor aggregates exhibit a high metastatic potential and could potentially serve as an important target for cancer therapies. In this study, we developed a microfluidic model that reconstitutes and is representative of the principal components of biological blood vessels, including vessel cavity, endothelium, and perivascular matrix containing chemokines. Using this model, the transendothelial invasion of tumor aggregates can be observed and recorded in realtime. In this study we analyzed the extravasation process of salivary gland adenoid cystic carcinoma (ACC) cell aggregates. ACC aggregates transmigrated across the endothelium under the stimulation of chemokine CXCL12. The endothelial integrity was irreversibly damaged at the site of transendothelial invasion. The transendothelial invasion of ACC aggregates was inhibited by AMD3100, but the adhesion of ACC aggregates to the endothelium was not affected by the CXCR4 antagonist. This model allows for detailed study of the attachment and transendothelial invasion of tumor aggregates; thus, it would be a useful tool for analysis of the underlying mechanisms of metastasis and for testing novel anti-metastasis agents.

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“…Microfluidic technologies have been used effectively to mimic components of the liver, 6 lung, 7,8 and heart, 9 recapitulating organ functions and processes that were otherwise unattainable with conventional macroscale systems. Microfluidics has been used to study various aspects of the vasculature and circulation, [10][11][12][13][14][15] but a platform that mimics multiple features of the complex vascular microenvironment has yet to be realized.…”

Section: Introductionmentioning

confidence: 99%

A microfluidic membrane device to mimic critical components of the vascular microenvironment

Srigunapalan¹,

Lam²,

Wheeler³

et al. 2011

Biomicrofluidics

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Vascular function, homeostasis, and pathological development are regulated by the endothelial cells that line blood vessels. Endothelial function is influenced by the integrated effects of multiple factors, including hemodynamic conditions, soluble and insoluble biochemical signals, and interactions with other cell types. Here, we present a membrane microfluidic device that recapitulates key components of the vascular microenvironment, including hemodynamic shear stress, circulating cytokines, extracellular matrix proteins, and multiple interacting cells. The utility of the device was demonstrated by measuring monocyte adhesion to and transmigration through a porcine aortic endothelial cell monolayer. Endothelial cells grown in the membrane microchannels and subjected to 20 dynes/ cm 2 shear stress remained viable, attached, and confluent for several days. Consistent with the data from macroscale systems, 25 ng/ml tumor necrosis factor ͑TNF͒-␣ significantly increased RAW264.7 monocyte adhesion. Preconditioning endothelial cells for 24 h under static or 20 dynes/ cm 2 shear stress conditions did not influence TNF-␣-induced monocyte attachment. In contrast, simultaneous application of TNF-␣ and 20 dynes/ cm 2 shear stress caused increased monocyte adhesion compared with endothelial cells treated with TNF-␣ under static conditions. THP-1 monocytic cells migrated across an activated endothelium, with increased diapedesis in response to monocyte chemoattractant protein ͑MCP͒-1 in the lower channel of the device. This microfluidic platform can be used to study complex cell-matrix and cell-cell interactions in environments that mimic those in native and tissue engineered blood vessels, and offers the potential for parallelization and increased throughput over conventional macroscale systems.

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Vascular mimetics based on microfluidics for imaging the leukocyte–endothelial inflammatory response

Cited by 122 publications

References 31 publications

SLIC‐1/sorting nexin 20: A novel sorting nexin that directs subcellular distribution of PSGL‐1

SLIC‐1/sorting nexin 20: A novel sorting nexin that directs subcellular distribution of PSGL‐1

A microfluidic-based device for study of transendothelial invasion of tumor aggregates in realtime

A microfluidic membrane device to mimic critical components of the vascular microenvironment

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