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Anti‐inflammatory, membrane‐stabilizing interactions of salmeterol with human neutrophils in vitro
Author(s) -
Anderson R.,
Feldman C.,
Theron A.J.,
Ramafi G.,
Cole P.J.,
Wilson R.
Publication year - 1996
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1996.tb15297.x
Subject(s) - salmeterol , chemistry , formoterol , pharmacology , superoxide , lysophosphatidylcholine , biochemistry , mechanism of action , in vitro , endocrinology , immunology , biology , phosphatidylcholine , phospholipid , enzyme , membrane , corticosteroid , asthma , budesonide
1 We have investigated the effects of salmeterol (0.3–50 μ) 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 μ) of salmeterol, while the responses of phorbol myristate acetate‐ and opsonised zymosan‐stimulated cells were affected only by higher concentrations (3–50 μ) 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 μ) of the pro‐oxidative, membrane‐destabilizing phospholipids, lysophosphatidylcholine (LPC), platelet activating factor (PAF) and lysoPAF (LPAF). 4 At concentrations of 6.25–50 μ salmeterol interfered with several other activities of stimulated neutrophils, including intracellular calcium fluxes, phospholipase A 2 activity and synthesis of PAF. 5 In an assay of membrane‐stabilizing activity, salmeterol (25 and 50 μ) neutralized the haemolytic action of LPC, PAF and LPAF. 6 Of the other commonly used β 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 β 2 ‐agonist properties of this agent.