Inhibitory effects of nedocromil sodium on the in vitro induced migration and leukotriene formation of human granulocytes.
Inflammatory cells, such as neutrophils and eosinophils, are thought to actively contribute to the pathogenesis of asthma since they infiltrate into the lung tissue and may be activated locally to release bronchoconstrictor mediators. In this study we provide evidence that nedocromil sodium is capable of effectively inhibiting the platelet-activating factor (PAF) and zymosan-activated serum (ZAS)-induced chemotaxis of polymorphonuclear granulocytes (PMN) [IC50 approximately 1 nmol/L and 0.1 mumol/L respectively]. The same inhibitory potency was obtained with sodium cromoglycate. Thus, nedocromil sodium may effectively inhibit the mobilisation of inflammatory cells in the lung. Furthermore, nedocromil sodium is capable of inhibiting the formation of the bronchoconstrictor mediator leukotriene-C4 (LTC4) by eosinophils in a concentration-dependent way [IC30 for A23187: 5.6 10(-5) mol/L; IC30 for opsonised zymosan (OZ): 6.3 10(-5) mol/L], whereas this drug is not capable of inhibiting leukotriene-B4 (LTB4) formation by neutrophils. These findings indicate that nedocromil sodium inhibits the release of bronchoconstrictor mediators not only from mast cells but also from eosinophils.
Bruijnzeel
P L
PL
Department of Pulmonary Disease, State University Hospital Utrecht, The Netherlands.
Warringa
R A
RA
Kok
P T
PT
Hamelink
M L
ML
Kreukniet
J
J
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000001:Calcimycin / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D004205:Cromolyn Sodium / Q000494:pharmacology; D004224:Diterpenes; D004804:Eosinophils / Q000187:drug effects; D046934:Ginkgolides; D006098:Granulocytes / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007783:Lactones / Q000494:pharmacology; D007975:Leukotriene B4 / Q000096:biosynthesis; D015289:Leukotrienes / Q000096:biosynthesis*; D017835:Nedocromil; D009504:Neutrophils / Q000187:drug effects; D010972:Platelet Activating Factor / Q000494:pharmacology; D015363:Quinolones / Q000494:pharmacology*; D013189:SRS-A / Q000096:biosynthesis; D015054:Zymosan / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004224:Diterpenes; D046934:Ginkgolides; D007783:Lactones; D015289:Leukotrienes; D010972:Platelet Activating Factor; D015363:Quinolones; D013189:SRS-A; D017835:Nedocromil; D007975:Leukotriene B4; D000001:Calcimycin; D015054:Zymosan; C045856:ginkgolide B; D004205:Cromolyn Sodium