Inhibition of platelet-activating factor (PAF)-induced chemotaxis and PAF binding to human eosinophils and neutrophils by the specific ginkgolide-derived PAF antagonist, BN 52021

• Published in: Journal of allergy and clinical immunology Vol. 83; no. 1; pp. 83 - 90
• Main Authors: Kurihara, K., Wardlaw, A.J., Moqbei, R., Kay, A.B.
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 1989; Elsevier
• Subjects: Albuterol - pharmacology; Biological and medical sciences; Chemotaxis, Leukocyte - drug effects; Dexamethasone - pharmacology; Diterpenes; Eosinophils - drug effects; Eosinophils - metabolism; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Ginkgolides; Humans; Immunobiology; Lactones - pharmacology; Modulation of the immune response (stimulation, suppression); Nedocromil; Neutrophils - drug effects; Neutrophils - metabolism; Platelet Activating Factor - antagonists & inhibitors; Platelet Activating Factor - metabolism; Platelet Activating Factor - pharmacology; Platelet Membrane Glycoproteins; Quinolones - pharmacology; Receptors, Cell Surface - drug effects; Receptors, G-Protein-Coupled; IC 50; M-NCF; PAF; fMLP; DMSO; SCG; LTB 4; HBSS; HPF; Human; Binding; Induction; Neutrophile; Antagonist; Inhibition; Chemotaxis; Eosinophil; Platelet activating factor
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/0091-6749(89)90480-6

We have investigated the effects of BN 52021 (a specific PAF antagonist derived from Ginkgo biloba) on PAF-induced human eosinophil and neutrophil chemotaxis. In response to an optimal concentration of PAF (10 −6 mol/L), the drug was significantly more potent ( p < 0.001) in inhibiting eosinophil as compared to neutrophil locomotion. These inhibitory effects were observed in a dose-dependent manner with a concentration of drug required to produce 50% inhibition of 7.0 (±2.2) × 10 −6 mol/L and 2.3 (±0.2) × 10 −5 mol/L for eosinophils and neutrophils, respectively. Sodium cromoglycate, nedocromil sodium, salbutamol, and dexamethasone (preincubated with cells up to 6 hours) had no effect over a wide dose range (10 −3 to 10 −9 mol/L). BN 52021 was significantly more effective in inhibiting chemotaxis when the cells were preincubated with the compound for up to 1 hour before commencement of the locomotion assay, whereas washing the cells completely abolished this effect. Inhibition by BN 52021 was specific for PAF in that it had no effect on chemotaxis induced by either leukotriene B 4, N-formyl-methionyl-leucyl-phenylalanine, or a purified human mononuclear cell-derived neutrophil chemotactic factor. BN 52021 also inhibited the specific binding of [ 3H]-PAF (10 −8 mol/L) to eosinophils and neutrophils in a concentration-dependent fashion with a concentration of drug required to produce 50% inhibition of 1.5 (± 0.3) × 10 −6 mol/L and 9.1 (±2.5) × 10 −7 mol/L, respectively. These results suggest that BN 52021 has potential as an anti-inflammatory agent in conditions associated with PAF-induced accumulation of neutrophils and eosinophils.