Nitric oxide-releasing compounds inhibit neutrophil adhesion to endothelial cells

Eur J Pharmacol. 1999 Oct 8;382(2):111-7. doi: 10.1016/s0014-2999(99)00581-6.


In the present work, we demonstrated that chemically different nitric oxide (NO)-releasing compounds inhibit tumor necrosis factor alpha (TNF-alpha)-induced polymorphonuclear leukocyte adhesion to endothelial cells in vitro. Two mesoionic oxatriazole derivatives GEA 3162 (1,2,3,4-oxatriazolium,5-amino-3(3, 4-dichlorophenyl)-chloride) and GEA 3175 (1,2,3,4-oxatriazolium, -3-(3-chloro-2-methylphenyl)-5-[[(4-methylphenyl)sulfonyl]amino]-, hydroxide inner salt) were compared to the earlier-known NO donor SIN-1 (3-morpholino-sydnonimine). GEA 3162 (3-10 microM) and GEA 3175 (10-30 microM) inhibited human polymorphonuclear leukocyte adhesion to B(4) endothelial cells in a dose-dependent manner being more potent than SIN-1. In the present model, leukocytes rather than endothelial cells seemed to be the target of the effect of NO. Flow cytometric analysis showed that NO-releasing compounds did not alter TNF-alpha induced CD11/CD18 surface expression in polymorphonuclear leukocytes. The inhibitory action of NO-releasing compounds on adhesion paralleled with the increased synthesis of cGMP in polymorphonuclear leukocytes. Analogues of cGMP inhibited polymorphonuclear leukocyte adhesion indicating a role for cGMP in the action of NO donors. The results suggest that exogenous NO in the form of NO-releasing compounds inhibits polymorphonuclear leukocyte adhesion to endothelial cells, which may be implicated in the regulation of leukocyte migration and leukocyte-mediated tissue injury.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD11 Antigens / biosynthesis
  • CD18 Antigens / biosynthesis
  • Cell Adhesion / drug effects*
  • Coculture Techniques
  • Cyclic GMP / analogs & derivatives
  • Cyclic GMP / metabolism
  • Cyclic GMP / pharmacology
  • Dose-Response Relationship, Drug
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / drug effects*
  • Humans
  • Molsidomine / analogs & derivatives
  • Molsidomine / pharmacology
  • Neutrophils / cytology
  • Neutrophils / drug effects*
  • Neutrophils / metabolism
  • Nitric Oxide Donors / pharmacology*
  • Rabbits
  • Thionucleotides / pharmacology
  • Triazoles / pharmacology
  • Tumor Necrosis Factor-alpha / pharmacology


  • CD11 Antigens
  • CD18 Antigens
  • GEA 3175
  • Nitric Oxide Donors
  • Thionucleotides
  • Triazoles
  • Tumor Necrosis Factor-alpha
  • 8-bromocyclic GMP
  • 8-((4-chlorophenyl)thio)cyclic-3',5'-GMP
  • linsidomine
  • GEA 3162
  • Molsidomine
  • Cyclic GMP