Dynamics of neutrophil extravasation and vascular permeability are uncoupled during aseptic cutaneous wounding

Min Ho Kim, Fitz Roy E Curry, Scott I. Simon

Research output: Contribution to journalArticlepeer-review

56 Scopus citations

Abstract

Transport of macromolecules and transmigration of leukocytes across vascular endothelium are regulated by a tight molecular junction, but the mechanisms by which these two inflammatory events are differentially controlled in time and magnitude during aseptic cutaneous wounding remain elusive. A real-time fluorescence imaging technique was developed to simultaneously track influx of Alexa 680-labeled albumin and genetically tagged enhanced green fluorescent proteinneutrophils [polymorphonuclear neutrophils (PMN)] within the wound bed. Vascular permeability increased approximately threefold more rapidly than the rate of PMN influx, reaching a maximum at 12 h, on the order of ∼0.15% per minute versus ∼0.05% per minute for PMN influx, which peaked at 18 h. Systemic depletion of PMN with antibody blocked their extravasation to the wound but did not alter the increase in vascular permeability. In contrast, pretreatment with antiplatelet GPIb decreased permeability by 25% and PMN influx by 50%. Hyperpermeability stimulated by the endotheliumspecific agonists VEGF or thrombin at 24 h postwounding was completely inhibited by blocking Rho-kinase-dependent signaling, whereas less inhibition was observed at 1 h and neutrophil influx was not perturbed. These data suggest that in aseptic wounds, the endothelium maintains a tight junctional barrier to protein leakage that is independent of neutrophil transmigration, partially dependent on circulating platelets, and associated with Rho-kinase-dependent signaling.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Cell Physiology
Volume296
Issue number4
DOIs
StatePublished - Apr 2009

Keywords

  • Enhanced green fluorescent protein-polymorphonuclear neutrophils
  • Platelets
  • Rho-kinase
  • Vascular endothelial growth factor

ASJC Scopus subject areas

  • Cell Biology
  • Physiology

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