Anti-inflammatory, membrane-stabilizing interactions of salmeterol with human neutrophils in vitro

Br J Pharmacol. 1996 Apr;117(7):1387-94. doi: 10.1111/j.1476-5381.1996.tb15297.x.


1. We have investigated the effects of salmeterol (0.3-50 microM) on several pro-inflammatory activities of human neutrophils in vitro. 2. Oxidant production by FMLP- and calcium ionophore (A23187)-activated neutrophils was particularly sensitive to inhibition by low concentrations (0.3-3 microM) of salmeterol, while the responses of phorbol myristate acetate- and opsonised zymosan-stimulated cells were affected only by higher concentrations (3-50 microM) of the drug. At these concentrations salmeterol is not cytotoxic, nor does it act as a scavenger of superoxide. 3. These anti-oxidative interactions of salmeterol with neutrophils were insensitive to propranolol but could be eliminated by washing the cells, or by pretreatment with low concentrations (1-2 microM) of the pro-oxidative, membrane-destabilizing phospholipids, lysophosphatidylcholine (LPC), platelet activating factor (PAF) and lysoPAF (LPAF). 4. At concentrations of 6.25-50 microM salmeterol interfered with several other activities of stimulated neutrophils, including intracellular calcium fluxes, phospholipase A2 activity and synthesis of PAF. 5. In an assay of membrane-stabilizing activity, salmeterol (25 and 50 microM) neutralized the haemolytic action of LPC, PAF and LPAF. 6. Of the other commonly used beta 2-adrenoceptor agonists, fenoterol, and formoterol, but not salbutamol, caused moderate inhibition of neutrophil oxidant generation by a superoxide-scavenging mechanism. However, unlike salmeterol, these agents possessed only weak membrane stabilizing properties. 7. We conclude that salmeterol antagonizes the pro-inflammatory, pro-oxidative activity of several bioactive lipids implicated in the pathogenesis of bronchial asthma, by a mechanism related to the membrane-stabilizing, rather than to the beta 2-agonist properties of this agent.

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Adrenergic beta-Agonists / pharmacology*
  • Adult
  • Albuterol / analogs & derivatives*
  • Albuterol / pharmacology
  • Anti-Inflammatory Agents / pharmacology*
  • Asthma / physiopathology
  • Calcium / metabolism
  • Cell Membrane / drug effects
  • Ethanolamines / pharmacology
  • Fenoterol / pharmacology
  • Formoterol Fumarate
  • Humans
  • In Vitro Techniques
  • NADH, NADPH Oxidoreductases / metabolism
  • Neutrophils / drug effects*
  • Neutrophils / enzymology
  • Neutrophils / metabolism
  • Oxygen Consumption / drug effects
  • Phospholipases A / metabolism
  • Phospholipases A2
  • Platelet Activating Factor / biosynthesis
  • Protein Kinase C / metabolism
  • Salmeterol Xinafoate
  • Superoxides / metabolism


  • Adrenergic beta-Agonists
  • Anti-Inflammatory Agents
  • Ethanolamines
  • Platelet Activating Factor
  • Superoxides
  • Fenoterol
  • Salmeterol Xinafoate
  • Adenosine Triphosphate
  • NADH, NADPH Oxidoreductases
  • Protein Kinase C
  • Phospholipases A
  • Phospholipases A2
  • Albuterol
  • Calcium
  • Formoterol Fumarate