Nitric oxide: an endogenous modulator of leukocyte adhesion

Proc Natl Acad Sci U S A. 1991 Jun 1;88(11):4651-5. doi: 10.1073/pnas.88.11.4651.


The objective of this study was to determine whether endogenous nitric oxide (NO) inhibits leukocyte adhesion to vascular endothelium. This was accomplished by superfusing a cat mesenteric preparation with inhibitors of NO production, NG-monomethyl-L-arginine (L-NMMA) or NG-nitro-L-arginine methyl ester (L-NAME), and observing single (30-microns diameter) venules by intravital video microscopy. Thirty minutes into the superfusion period the number of adherent and emigrated leukocytes, the erythrocyte velocity, and the venular diameter were measured; venular blood flow and shear rate were calculated from the measured parameters. The contribution of the leukocyte adhesion glycoprotein CD11/CD18 was determined using the CD18-specific monoclonal antibody IB4. Both inhibitors of NO production increased leukocyte adherence more than 15-fold. Leukocyte emigration was also enhanced, whereas venular shear rate was reduced by nearly half. Antibody IB4 abolished the leukocyte adhesion induced by L-NMMA and L-NAME. Incubation of isolated cat neutrophils with L-NMMA, but not L-NAME, resulted in direct upregulation of CD11/CD18 as assessed by flow cytometry. Decrements in venular shear rate induced by partial occlusion of the superior mesenteric artery in untreated animals revealed that only a minor component of L-NAME-induced leukocyte adhesion was shear rate-dependent. The L-NAME-induced adhesion was inhibited by L-arginine but not D-arginine. These data suggest that endothelium-derived NO may be an important endogenous modulator of leukocyte adherence and that impairment of NO production results in a pattern of leukocyte adhesion and emigration that is characteristic of acute inflammation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens, CD / analysis
  • Arginine / analogs & derivatives*
  • Arginine / pharmacology
  • CD11 Antigens
  • CD18 Antigens
  • Cats
  • Cell Adhesion* / drug effects
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / physiology*
  • NG-Nitroarginine Methyl Ester
  • Neutrophils / drug effects
  • Neutrophils / immunology
  • Neutrophils / physiology*
  • Nitric Oxide / metabolism*
  • Splanchnic Circulation
  • Tetradecanoylphorbol Acetate / pharmacology
  • Venules / physiology
  • omega-N-Methylarginine


  • Antigens, CD
  • CD11 Antigens
  • CD18 Antigens
  • omega-N-Methylarginine
  • Nitric Oxide
  • Arginine
  • Tetradecanoylphorbol Acetate
  • NG-Nitroarginine Methyl Ester