Inhibition of neutrophil and eosinophil induced chemotaxis by nedocromil sodium and sodium cromoglycate

Abstract

1. Neutrophils and eosinophils infiltrate the airways in association with the allergen-induced late phase asthmatic reaction. Mobilization of these cells takes place via lipid-like and protein-like chemotactic factors. In this study platelet-activating factor (PAF), leukotriene B4 (LTB4), zymosan-activated serum (ZAS) and N-formyl-methionyl-leucyl-phenylalanine (FMLP) were used as illustrative examples of both groups. Chemotaxis was studied in human neutrophils and eosinophils. The inhibitory effects of nedocromil sodium and sodium cromoglycate were evaluated. 2. All chemotactic factors tested attracted neutrophils with the following rank order of activity: ZAS > PAF ≡ FMLP ≡ LTB4. Eosinophils were only mobilized by PAF, LTB4 and ZAS with the following rank order of activity: ZAS > PAF > LTB4. 3. Nedocromil sodium and sodium cromoglycate were equally active as the PAF antagonist BN 52021 in inhibiting the PAF-induced chemotaxis of neutrophils (IC50 ~ 10-8 M). Both drugs were also equally active in inhibiting the chemotaxis of neutrophils induced by ZAS (IC50 ~ 10-7-10-6 M), FMLP (IC50 ~ 10-7 M) and LTB4 (IC50 ~ 10-6 M). 4. Nedocromil sodium significantly inhibited the chemotaxis of eosinophils induced by PAF (IC50 ~ 10-6 M) and LTB4 (IC50 ~ 10-7 M). The inhibitory potency of BN 52021 was similar to that of nedocromil sodium on the PAF-induced chemotaxis of eosinophils. Sodium cromoglycate was incapable of eliciting significant inhibition of these chemotactic responses. However, sodium cromoglycate significantly inhibited the chemotaxis of eosinophils induced by ZAS (IC50 ~ 10-7 M), whereas nedocromil sodium was ineffective.