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Real-time Imaging of Endothelial Cell-cell Junctions During Neutrophil Transmigration Under Physiological Flow
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Localized signals that regulate transendothelial migration.

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  • 1Department of Pathology, Northwestern University Feinberg School of Medicine, 303 East Chicago Avenue, Chicago, IL 60201, USA.

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Summary
This summary is machine-generated.

Transendothelial migration (TEM) is crucial for leukocyte emigration during inflammation. This review highlights how PECAM and CD99 adhesion molecules regulate TEM signaling pathways involving calcium flux and membrane trafficking.

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Area of Science:

  • Immunology
  • Cell Biology
  • Physiology

Background:

  • Transendothelial migration (TEM) is a critical step in leukocyte emigration, essential for inflammatory responses.
  • Recent advancements have elucidated key molecular mechanisms regulating TEM.
  • Adhesion molecules PECAM (CD31) and CD99 play pivotal roles in orchestrating TEM.

Purpose of the Study:

  • To review recent developments in understanding the signaling pathways governing TEM.
  • To highlight the roles of PECAM and CD99 in regulating TEM.
  • To discuss the mechanisms of membrane trafficking and VE-cadherin dynamics during TEM.

Main Methods:

  • Review of existing literature on leukocyte transendothelial migration.
  • Analysis of signaling pathways initiated by PECAM and CD99.
  • Examination of calcium flux and membrane trafficking events.
  • Investigation of VE-cadherin regulation during TEM.

Main Results:

  • PECAM initiates a signaling pathway for calcium flux, essential for TEM, involving TRPC6 channels and lateral border recycling compartment (LBRC) membrane trafficking.
  • CD99 signals via soluble adenylate cyclase and protein kinase A, recruiting a second wave of LBRC trafficking.
  • Transient removal of VE-cadherin is critical for TEM, regulated by distinct signaling pathways compared to vascular permeability.

Conclusions:

  • PECAM and CD99 are key regulators of TEM through distinct signaling cascades.
  • Calcium influx and sequential membrane trafficking are vital for leukocyte passage across the endothelium.
  • Understanding these pathways offers insights into controlling inflammatory responses.