Inhibition of human neutrophil activation by the allergic mediator release inhibitor, CI-949.

The allergic mediator release inhibitor CI-949 [5-methoxy-3-(1-methylethoxy)-1-phenylN-1H-tetrazol-5-yl-1H-indole-2-carboxamide, L-arginine salt] was evaluated for its effects on human neutrophil functions. Cl-949 (100 pM) inhibited spontaneous migration and chemotaxis toward f-met-Ieu-phe (FMLP) by 49.1% and 45.8%, respectively. At the same concentration, CI-949 inhibited the phagocytosis of serum-opsonized zymosan (SOZ) by 39.0%. CI-949 inhibited leukotriene B4 and thromboxane B2 release in response to SOZ with lC50sof 2.0 p.M and 3.3 �M, while inhibiting the response to FMLP with lC50sof 1.7 and 2.0 �M. CI-949 also inhibited myeloperoxidase release from primary lysosomal