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A Microphysiological System to Study Leukocyte-Endothelial Cell Interaction during Inflammation
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Inflammation-Sensitive Myosin-X Functionally Supports Leukocyte Extravasation by Cdc42-Mediated ICAM-1-Rich

Jeffrey Kroon1, Antje Schaefer1, Jos van Rijssel1

  • 1Molecular Cell Biology Laboratory, Department of Plasma Proteins, Sanquin Research and Landsteiner Laboratory, Academic Medical Center Amsterdam, University of Amsterdam, 1066 CX Amsterdam, the Netherlands.

Journal of Immunology (Baltimore, Md. : 1950)
|February 2, 2018
PubMed

Insights

Endothelial filopodia, rich in ICAM-1, act as adhesive sites for leukocytes during inflammation, facilitating their transition from rolling to crawling. Their regulation is crucial for leukocyte extravasation under flow conditions.

Area of Science:

  • Cell biology
  • Immunology
  • Vascular biology

Background:

  • Leukocyte transendothelial migration is critical for inflammatory responses.
  • Inflamed endothelial cells develop finger-like protrusions of unclear function.
  • Leukocyte adhesion initiates their extravasation process.

Purpose of the Study:

  • To identify the nature and function of endothelial finger-like protrusions.
  • To elucidate the molecular mechanisms regulating these structures.
  • To determine the role of these structures in leukocyte extravasation.

Main Methods:

  • Immunofluorescence microscopy to visualize ICAM-1 and F-actin.
  • Functional assays to assess leukocyte adhesion and migration.
  • Molecular analyses of myosin-X, Cdc42, and PAK4 involvement.
  • Analysis of myosin-X regulation by TNF-α and JNK signaling.

Main Results:

  • Endothelial finger-like protrusions are identified as ICAM-1 and F-actin-rich filopodia.
  • These filopodia function as adhesive structures, mediating leukocyte rolling-to-crawling transition.
  • Myosin-X, Cdc42, and PAK4 are essential for filopodia formation and function.
  • Myosin-X expression is regulated by TNF-α/JNK signaling and increased in atherosclerosis.

Conclusions:

  • Endothelial filopodia are key regulators of leukocyte adhesion initiation under flow.
  • Myosin-X is a critical mediator of endothelial filopodia in leukocyte extravasation.
  • Understanding filopodia regulation offers insights into inflammatory diseases like atherosclerosis.

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