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Updated: Jul 4, 2026

Quantitative In vitro Assay to Measure Neutrophil Adhesion to Activated Primary Human Microvascular Endothelial Cells under Static Conditions
11:22

Quantitative In vitro Assay to Measure Neutrophil Adhesion to Activated Primary Human Microvascular Endothelial Cells under Static Conditions

Published on: August 23, 2013

Intercellular adhesion molecule-1-dependent neutrophil adhesion to endothelial cells induces caveolae-mediated

Guochang Hu1, Stephen M Vogel, David E Schwartz

  • 1Department of Pharmacology, University of Illinois College of Medicine, 835 S Wolcott Ave, Chicago, IL 60612, USA.

Circulation Research
|May 31, 2008
PubMed

Insights

Polymorphonuclear neutrophils (PMNs) increase lung vascular permeability via caveolin-1 signaling. Blocking PMN interaction with endothelial cells via ICAM-1 prevents this, highlighting a therapeutic target for lung injury.

Area of Science:

  • Cell biology
  • Pulmonary medicine
  • Immunology

Background:

  • Pulmonary vascular permeability and edema are critical in acute lung injury.
  • Polymorphonuclear neutrophils (PMNs) play a key role in initiating these responses.
  • The precise molecular mechanisms underlying PMN-induced hyperpermeability are not fully understood.

Purpose of the Study:

  • To investigate the role of caveolae and caveolin-1 in PMN-induced pulmonary vascular hyperpermeability.
  • To elucidate the signaling pathways involved in PMN-endothelial cell interactions leading to increased permeability.
  • To explore potential therapeutic targets for PMN-mediated lung injury.

Main Methods:

  • Utilized caveolin-1 knockout mice and gene silencing in rats to assess the necessity of caveolin-1.
  • Investigated the role of Src phosphorylation of caveolin-1 in caveolae-mediated endocytosis.
  • Employed an intercellular adhesion molecule (ICAM)-1 blocking antibody to study PMN-endothelial cell binding.
  • Used direct ICAM-1 activation to confirm its role in signaling.

Main Results:

  • PMN-induced increase in lung vascular permeability requires caveolin-1.
  • Permeability increases were abolished in caveolin-1 knockout mice and suppressed by silencing caveolin-1.
  • The response depended on Src phosphorylation of caveolin-1, activating caveolae-mediated endocytosis.
  • Blocking ICAM-1-mediated PMN binding abrogated Src phosphorylation and endothelial permeability increases.
  • Direct ICAM-1 activation mimicked these effects, indicating ICAM-1 initiates caveolin-1 signaling.

Conclusions:

  • Pulmonary vascular hyperpermeability induced by activated PMNs relies significantly on caveolin-1 signaling.
  • ICAM-1 activation of PMNs triggers caveolin-1-dependent signaling, leading to increased caveolae-mediated transcytosis and hyperpermeability.
  • The transendothelial vesicular permeability pathway is a crucial contributor to edema formation in PMN-mediated lung injury, representing a potential therapeutic target.

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