Nitric oxide regulates interactions of PMN with human brain microvessel endothelial cells

Biochem Biophys Res Commun. 2004 Oct 8;323(1):142-8. doi: 10.1016/j.bbrc.2004.08.062.


The hypothesis that the NO/cGMP pathway modulates PMN adhesion to human brain microvessel endothelial cells (HBMEC) was examined. Human PMN were incubated with resting or TNF-alpha-treated endothelial monolayers, and adhesion was quantified by light microscopy. TNF-alpha upregulated PMN adhesion in a time-dependent manner. Treatment of HBMEC with the NO donors SNP and DETA NONOate for 4 or 24 h decreased PMN adhesion. This was completely reversed by the guanylyl cyclase inhibitor ODQ, while addition of a cGMP agonist (8-Br-cGMP) decreased PMN adhesion. NO donors did not affect the levels of E-selectin or ICAM-1 in HBMEC. However, pre-treatment of PMN with NO donors or 8-Br-cGMP decreased their adhesion to recombinant E-selectin and ICAM-1, suggesting an effect of NO on PMN. These findings indicate that NO modulates PMN-HBMEC interactions through cGMP and decreases the binding of PMN to the adhesion molecules E-selectin and ICAM-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Brain / blood supply*
  • Cell Adhesion
  • Cells, Cultured
  • Cyclic GMP-Dependent Protein Kinases / metabolism
  • E-Selectin / metabolism
  • Endothelial Cells / cytology*
  • Endothelium, Vascular / cytology*
  • Humans
  • Inflammation
  • Intercellular Adhesion Molecule-1 / metabolism
  • Microcirculation
  • Models, Biological
  • Neutrophils / metabolism*
  • Nitric Oxide / metabolism*
  • Nitroso Compounds / pharmacology
  • Signal Transduction
  • Time Factors
  • Tumor Necrosis Factor-alpha / metabolism
  • Up-Regulation


  • E-Selectin
  • Nitroso Compounds
  • Tumor Necrosis Factor-alpha
  • Intercellular Adhesion Molecule-1
  • 2,2'-(hydroxynitrosohydrazono)bis-ethanamine
  • Nitric Oxide
  • Cyclic GMP-Dependent Protein Kinases