A soluble gradient of the neuropeptide secretoneurin promotes the transendothelial migration of monocytes in vitro

Secretoneurin, derived from the chromogranin secretogranin II, triggers the selective migration of human monocytes, eosinophils, fibroblasts, endothel ial and smooth muscle cells. More recently, we located specific binding sit es on the human monocytic cell line MonoMac-6. Differentiated U937 transend othelial diapedesis was evaluated using an in vitro model of the vascular w all and specific monoclonal antibodies against CD11/CD18 and the or-chains of the very late activation antigen (VLA)-4 were used to evaluate involved adhesion molecules. Results showed a significant migratory response to secr etoneurin between 10(-8) to 10(-10) M. Migration was comparable to a maxima l effect induced by the monocyte chemotactic agent N-formyl-Met-Leu-Phe (fM LP, 10(-8) M). Rabbit anti-secretoneurin antibodies were able to block the neuropeptide effect but not of fMLP and a trypsinized secretoneurin prepara tion as well as the secretogranin II-fragment EL-17 were ineffective in eli citing migration. Transmigration of U937 across endothelial-layers toward s ecretoneurin is inhibited by antibodies to CD11/CD18 adhesion molecules. Th e novel neuropeptide secretoneurin may play a role in regulating migration of monocytes into the subendothelial space, supposing a role in inflammator y responses. (C) 1999 Elsevier Science B.V. All rights reserved.