Nitric oxide inhibits neutrophil migration by a mechanism dependent on ICAM-1: role of soluble guanylate cyclase

Nitric Oxide. 2006 Aug;15(1):77-86. doi: 10.1016/j.niox.2006.02.004. Epub 2006 Apr 18.


In the present study, we addressed the role of intercellular adhesion molecule type 1 (ICAM-1/CD54) in neutrophil migration to inflammatory site and whether the inhibitory effect of nitric oxide (NO) upon the neutrophil rolling, adhesion and migration involves down-modulation of ICAM-1 expression through a cyclic GMP (cGMP) dependent mechanism. It was observed that neutrophil migration induced by intraperitoneal administration of endotoxin (LPS), carrageenan (Cg) or N-formyl peptide (fMLP) in ICAM-1 deficient (ICAM-1-/-) is similar to that observed in wild type (WT) mice. The treatment of mice with NO synthase (NOS) inhibitors, NG-nitro-l-arginine, aminoguanidine or with a soluble guanylate cyclase (sGC) inhibitor, ODQ enhanced LPS- or Cg-induced neutrophil migration, rolling and adhesion on venular endothelium. These parameters induced by LPS were also enhanced by 1400 W, a specific iNOS inhibitor, treatment. On the other hand, the treatment of the mice with S-nitroso-N-acetylpenicillamine (SNAP), an NO donor, reduced these parameters induced by LPS or Cg by a mechanism sensitive to ODQ pretreatment. The NOS inhibitors did not enhance LPS-, Cg- or fMLP-induced migration and adhesion in ICAM-1-/- mice. Moreover, genetic (iNOS-/- mice) or pharmacological inhibition of NOS or of sGC enhanced LPS-induced ICAM-1 expression on mesenteric microcirculation vessels of WT mice. By contrast, SNAP reduced the ICAM-1 expression by a mechanism dependent on cGMP. In conclusion, the results suggest that although during inflammation, ICAM-1 does not contribute to neutrophil migration, it is necessary for the down-modulatory effect of inflammation-released NO on the adhesion and transmigration of neutrophils. Moreover, these NO effects are mediated via cGMP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carrageenan / pharmacology
  • Cell Adhesion / drug effects
  • Cell Movement / drug effects*
  • Guanylate Cyclase / antagonists & inhibitors
  • Guanylate Cyclase / metabolism
  • Intercellular Adhesion Molecule-1 / genetics
  • Intercellular Adhesion Molecule-1 / physiology*
  • Leukocyte Rolling / drug effects
  • Lipopolysaccharides / pharmacology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • N-Formylmethionine Leucyl-Phenylalanine / pharmacology
  • Neutrophils / cytology*
  • Neutrophils / drug effects
  • Nitric Oxide / metabolism*
  • Nitric Oxide Donors / pharmacology
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Nitric Oxide Synthase / metabolism
  • S-Nitroso-N-Acetylpenicillamine / pharmacology
  • Splanchnic Circulation / drug effects


  • Icam1 protein, mouse
  • Lipopolysaccharides
  • Nitric Oxide Donors
  • Intercellular Adhesion Molecule-1
  • Nitric Oxide
  • N-Formylmethionine Leucyl-Phenylalanine
  • S-Nitroso-N-Acetylpenicillamine
  • Carrageenan
  • Nitric Oxide Synthase
  • Guanylate Cyclase