Signaling in neuropeptide-induced migration of human eosinophils

At inflammatory sites, leukocytes may confront multiple, competing chemoatt ractive signals. We compared the chemotactic potencies of several sensory n europeptides with regard to signal transduction pathways in eosinophils, Eo sinophils were enriched using magnetic cell sorting and migration was assay ed in a Boyden microchemotaxis chamber, We found stimulatory effects of sub stance P, calcitonin gene-related peptide (CGRP), secretoneurin, vasoactive intestinal peptide (VIP), and secretin on eosinophil migration, Actions of VIP are predominantly mediated via VIP receptor type I. Migration toward s ecretoneurin, VIP, and secretin was blocked by a phosphodiesterase inhibito r, which, in contrast failed to affect substance P- and CGRP-induced eosino phil chemotaxis. Wortmannin blunted the migratory responses induced by all neuropeptides tested and substance P-induced effects on eosinophils were ty rphostin-23-sensitive. We conclude that substance P CGRP, secretoneurin, an d VIP/secretin stimulate eosinophil migration involving wortmannin-sensitiv e enzymes, Moreover, secretoneurin and VIP/secretin require additional acti vation of phosphodiesterases to stimulate eosinophil migration.