Inhibition of eosinophil chemotaxis by chronic blockade of nitric oxide biosynthesis

Eur J Pharmacol. 1996 Aug 29;310(2-3):201-7. doi: 10.1016/0014-2999(96)00379-2.


The effect of chronic N omega-nitro-L-arginine methyl ester (L-NAME) treatment on the in vivo eosinophil migration induced by bradykinin, platelet-activating factor (PAF), lipopolysaccharide and carrageenin has been investigated in the rat using the pleurisy model. The in vitro (microchemotaxis chamber) eosinophil migration induced by N-formyl-methionyl-leucyl-phenylalanine (fMLP), PAF and zymosan-activated serum was also evaluated in the rat. The eosinophils were obtained from the peritoneal cavity of male Wistar rats and isolated on a discontinuous metrizamide gradient. Chronic inhibition of nitric oxide biosynthesis was achieved by adding L-NAME to the drinking water to give an intake of approximately 75 mumol/rat/day for 4 weeks. Rats treated chronically with L-NAME developed a significant level of hypertension (163 +/- 4.8 mmHg; P < 0.01) compared with animals which received either the same dose of the inactive enantiomer D-NAME (124 +/- 3.2 mmHg) or tap water alone (119 +/- 1.6 mmHg). The intrapleural injection of bradykinin (50 micrograms), PAF (1 microgram), lipopolysaccharide (0.25 microgram) and carrageenin (125 micrograms) into untreated rats in vivo induced a significant level of eosinophil migration by 24 h post-injection. This migration was markedly reduced in L-NAME-treated rats. Eosinophils obtained from untreated rats showed a significant level of migration in vitro in response to fMLP (5 X 10(-8) M), PAF (10(-8) M) and zymosan-activated serum (27 microliters). In contrast, the migration induced by these chemotactic agents was markedly reduced in cells isolated from animals treated chronically with L-NAME. L-Arginine (5.5 mM), but not D-arginine (5.5 mM), restored the ability of eosinophils from L-NAME-treated animals to migrate in response to fMLP. Our results indicate that nitric oxide plays a major role in the in vivo and ex vivo migration of eosinophils.

MeSH terms

  • Animals
  • Bradykinin / pharmacology
  • Carrageenan / pharmacology
  • Chemotaxis, Leukocyte / drug effects*
  • Enzyme Inhibitors / pharmacology*
  • Leukocyte Count
  • Lipopolysaccharides / pharmacology
  • Male
  • N-Formylmethionine Leucyl-Phenylalanine / pharmacology
  • NG-Nitroarginine Methyl Ester / pharmacology*
  • Nitric Oxide / antagonists & inhibitors*
  • Nitric Oxide / biosynthesis
  • Platelet Activating Factor / pharmacology
  • Pleura / cytology
  • Rats
  • Rats, Wistar


  • Enzyme Inhibitors
  • Lipopolysaccharides
  • Platelet Activating Factor
  • Nitric Oxide
  • N-Formylmethionine Leucyl-Phenylalanine
  • Carrageenan
  • Bradykinin
  • NG-Nitroarginine Methyl Ester