INTERLEUKIN (IL)-8-INDUCED INVITRO HUMAN LYMPHOCYTE MIGRATION IS INHIBITED BY CHOLERA AND PERTUSSIS TOXINS AND INHIBITORS OF PROTEIN KINASE-C

To further investigate the intracellular mechanisms involved in IL-8-induced human mixed peripheral blood lymphocyte (PBL) migration, the effects of pertussis toxin (PTX), cholera toxin (CTX), and protein kinase C (pkC) inhibitors were investigated. Potent inhibition of IL-8-induced PBL migration was observed following exposure of PBL to PTX and CTX (1pM to 0.1μM), 8-bromo cyclic adenosine monophosphate (cAMP; 1nM to 1μM), H7 (1 pM to 0.1μM), sphingosine (0.1μM to 100μM) and the novel pkC inhibitors Ro 31-7549 and Ro 31-8220 (10pM to 1μM) for 10 min. Following incubation of the lymphocytes for 30 min in the presence of the direct activators of pkC, 1-oleoyl-2-acetyl-sn-glycerol (OAG) and 1,2-dioctanoyl-sn-glycerol (DOG; 10nM to 100μM), there was a reversal of the effects of a suboptimal dose of the specific pkC inhibitors Ro 31-7549 and Ro 31-8220. These results suggest that intracellular signals transduced during IL-8-induced in vitro PBL migration may involve pertussis and cholera toxin-sensitive G protein subunits and activation of pkC, processes which are characteristically linked to receptor binding. © 1990.