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, endothelial and smooth muscle cells. More recently, we located specific binding sites on the human monocytic cell line MonoMac-6. Differentiated U937 transendothelial diapedesis was evaluated using an in vitro model of the vascular wall and specific monoclonal antibodies against CD11/CD18 and the alpha-chains of the very late activation antigen (VLA)-4 were used to evaluate involved adhesion molecules. Results showed a significant migratory response to secretoneurin between 10(-8) to 10(-10) M. Migration was comparable to a maximal effect induced by the monocyte chemotactic agent N-formyl-Met-Leu-Phe (fMLP, 10(-8) M). Rabbit anti-secretoneurin antibodies were able to block the neuropeptide effect but not of fMLP and a trypsinized secretoneurin preparation as well as the secretogranin II-fragment EL-17 were ineffective in eliciting migration. Transmigration of U937 across endothelial-layers toward secretoneurin is inhibited by antibodies to CD11/CD18 adhesion molecules. The novel neuropeptide secretoneurin may play a role in regulating migration of monocytes into the subendothelial space, supposing a role in inflammatory responses.
Kähler
C M
CM
Department of Internal Medicine, Faculty of Medicine, University of Innsbruck, Austria.
Kaufmann
G
G
Hogue-Angeletti
R
R
Fischer-Colbrie
R
R
Dunzendorfer
S
S
Reinisch
N
N
Wiedermann
C J
CJ
D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D015703:Antigens, CD / Q000276:immunology; D018845:CD11 Antigens / Q000276:immunology; D018821:CD18 Antigens / Q000276:immunology; D002417:Cattle; D002465:Cell Movement / Q000187:drug effects*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D003101:Collodion; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D005374:Filtration / Q000295:instrumentation; D006801:Humans; D039441:Integrin alpha4; D007700:Kinetics; D009000:Monocytes / Q000166:cytology / Q000187:drug effects*; D009479:Neuropeptides / Q000276:immunology / Q000494:pharmacology*; D053381:Secretogranin II; D020298:U937 Cells