Secretoneurin (SN) induces monocyte chemotaxis through a pertussis toxin-(PT) signaling pathway

Secretoneurin (SN). a 33-amino acid peptide cleaved from the neuroendocrine secretory protein secretogranin II (chromogranin C), induces chemotaxis of monocytes but not neutrophils. In the present study we examined effects of signaling inhibitors on SN-induced monocyte migration. Both PT and CT inhibited SN-induced chemotaxis in a dose-dependent fashion; the ED50 for PT was 20ng/ml, and 300ng/ml for CT. 8-bromo-cAMP also blocked migration, consistent with CT inhibition mediated by cAMP. We also examined whether protein kinase (PK) inhibitors could block migration of monocyte chemotaxis. The PKC inhibitor bisindolymaleimide, along with the tyrosine kinase inhibitor genistein, blocked SN stimulation. Finally, we examined whether SN increased cytosolic Ca+2. Untike classical chemoattractants, such as fMLP or MCP-1, SN did not increase Ca+2 levels. Our studies suggest that SN signals through a G-protein-coupled pathway to stimulate either tyrosine or serine-threonine kinases, that in turn induce cellular movement.