title: Inhibition of platelet-activating factor- and zymosan-activated serum-induced chemotaxis of human neutrophils by nedocromil sodium, BN 52021 and sodium cromoglycate.
abstract: 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 (IC50 approximately 1 nM). 3. Nedocromil sodium and sodium cromoglycate were equally potent in inhibiting ZAS-induced neutrophil chemotaxis (IC50 = 0.1-1 microM), whereas BN 52021 was considerably less potent (IC30 = 10 microM). 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 Ca2+-mobilization was investigated. BN 52021, at a concentration of 100 microM, completely inhibited Paf-induced Ca2+-mobilization and inhibited ZAS-induced Ca2+-mobilization by about 50%. Nedocromil sodium and sodium cromoglycate were ineffective.
authors.affiliation: Department of Pulmonary Disease, State University Hospital Utrecht, The Netherlands.
authors.forename: P L
authors.initials: PL
authors.lastname: Bruijnzeel
authors.forename: R A
authors.initials: RA
authors.lastname: Warringa
authors.forename: P T
authors.initials: PT
authors.lastname: Kok
mesh_terms: D002118:Calcium / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D004205:Cromolyn Sodium / Q000494:pharmacology*; D004224:Diterpenes; D046934:Ginkgolides; D006098:Granulocytes / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007783:Lactones / Q000494:pharmacology*; D017835:Nedocromil; D009504:Neutrophils / Q000187:drug effects*; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D015363:Quinolones / Q000494:pharmacology*; D015054:Zymosan / Q000037:antagonists & inhibitors*
chemical_list: D004224:Diterpenes; D046934:Ginkgolides; D007783:Lactones; D010972:Platelet Activating Factor; D015363:Quinolones; D017835:Nedocromil; D015054:Zymosan; C045856:ginkgolide B; D004205:Cromolyn Sodium; D002118:Calcium