Inhibition of platelet-activating factor- and zymosan-activated serum-induced chemotaxis of human neutrophils by nedocromil sodium, BN 52021 and sodium cromoglycate.
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.
Bruijnzeel
P L
PL
Department of Pulmonary Disease, State University Hospital Utrecht, The Netherlands.
Warringa
R A
RA
Kok
P T
PT
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*
D004224:Diterpenes; D046934:Ginkgolides; D007783:Lactones; D010972:Platelet Activating Factor; D015363:Quinolones; D017835:Nedocromil; D015054:Zymosan; C045856:ginkgolide B; D004205:Cromolyn Sodium; D002118:Calcium