Cutting edge: peripheral neuropeptides attract immature and arrest mature blood-derived dendritic cells.
Dendritic cells (DC) are highly motile and play a key role in mediating immune responses in various tissues and lymphatic organs. We investigated locomotion of mononuclear cell-derived DC at different maturation stages toward gradients of sensory neuropeptides in vitro. Calcitonin gene-related peptide, vasoactive intestinal polypeptide, secretin, and secretoneurin induced immature DC chemotaxis comparable to the potency of RANTES, whereas substance P and macrophage-inflammatory protein-3beta stimulated immature cell migration only slightly. Checkerboard analyses revealed a true chemotactic response induced by neuropeptides. Upon maturation of DC, neuropeptides inhibited spontaneous, macrophage-inflammatory protein-3beta- and 6Ckine-induced cell migration. Maturation-dependent changes in migratory behavior coincided with distinct neuropeptide-induced signal transduction in DC. Peripheral neuropeptides might guide immature DC to peripheral nerve fibers where high concentrations of these peptides can arrest the meanwhile matured cells. It seems that one function of sensory nerves is to fasten DC at sites of inflammation.
Dunzendorfer
S
S
Divisions of General Internal Medicine, Department of Internal Medicine, University of Innsbruck, Innsbruck, Austria.
Kaser
A
A
Meierhofer
C
C
Tilg
H
H
Wiedermann
C J
CJ
D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002469:Cell Separation; D002478:Cells, Cultured; D002630:Chemotactic Factors / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000276:immunology*; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D016130:Immunophenotyping; D009000:Monocytes / Q000166:cytology; D009479:Neuropeptides / Q000494:pharmacology*; D012633:Secretin / Q000494:pharmacology; D053381:Secretogranin II; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
D002630:Chemotactic Factors; D009479:Neuropeptides; D053381:Secretogranin II; D012633:Secretin; C081159:secretoneurin; D014660:Vasoactive Intestinal Peptide; D015740:Calcitonin Gene-Related Peptide