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Inhibition of platelet‐activating factor‐ and zymosan‐activated serum‐induced chemotaxis of human neutrophils by nedocromil sodium, BN 52021 and sodium cromoglycate
Author(s) -
Bruijnzeel P.L.B.,
Warringa R.A.J.,
Kok P.T.M.
Publication year - 1989
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.1476-5381.1989.tb12586.x
Subject(s) - nedocromil sodium , zymosan , nedocromil , chemotaxis , platelet activating factor , chemistry , pharmacology , platelet , sodium , immunology , medicine , biochemistry , in vitro , receptor , respiratory disease , alternative medicine , organic chemistry , pathology , lung , placebo
1 Inflammatory cells such as eosinophils and neutrophils are thought to contribute actively to the pathogenesis of asthma since they infiltrate into the lung tissue. These cells are mobilized by lipid‐like and protein‐like chemotactic factors. As illustrative examples of both groups, platelet‐activating‐factor (Paf) and zymosan‐activated‐serum (ZAS) were used in this study. The inhibitory effects of nedocromil sodium, the Paf antagonist BN 52021 and sodium cromoglycate on Paf‐ and ZAS‐induced neutrophil chemotaxis were evaluated. 2 All tested drugs inhibited Paf‐induced neutrophil chemotaxis with approximately the same potency (IC 50 ≅ 1 n m ). 3 Nedocromil sodium and sodium cromoglycate were equally potent in inhibiting ZAS‐induced neutrophil chemotaxis (IC 50 = 0.1–1 μ m ), whereas BN 52021 was considerably less potent (IC 30 =10 μ m ). 4 To find out whether the drugs tested could inhibit early events in cell activation, their capacity to inhibit Paf‐ and ZAS‐induced cytosolic free Ca 2+ ‐mobilization was investigated. BN 52021, at a concentration of 100 μ m , completely inhibited Paf‐induced Ca 2+ ‐mobilization and inhibited ZAS‐induced Ca 2+ ‐mobilization by about 50%. Nedocromil sodium and sodium cromoglycate were ineffective.