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.