SECRETONEURIN-INDUCED IN-VITRO CHEMOTAXIS OF HUMAN MONOCYTES IS INHIBITED BY PERTUSSIS TOXIN AND AN INHIBITOR OF PROTEIN-KINASE-C

The sensory neuropeptide secretoneurin (SN) triggers chemotactic migra tion of monocytes. We have investigated the possibility that SN, like other chemoattractants such as formyl-Met-Leu-Phe and chemokines, migh t stimulate migration of monocytes by G protein and protein kinase C ( PKC) activation and induce Ca-i(2+) release. We report that preincubat ion of monocytes with pertussis toxin inhibited SN chemotaxis. Stauros porine, an inhibitor of PKC, significantly decreased SN-induced chemot axis of monocytes, suggesting that PKC may be involved in the signalin g. Tyrphostin-23, which inhibits tyrosin kinase, did not affect SN-ind uced chemotaxis of monocytes. This suggests that SN uses a signaling m echanism that is coupled to pertussis toxin-sensitive G proteins. Invo lvement of phospholipase C beta as a result of PKC activation is sugge sted by a SN-induced increase of intracellular Ca2+ concentration in m onocytes.