MIP-3 alpha induces human eosinophil migration and activation of the mitogen-activated protein kinases (p42/p44 MAPK)

The CC chemokine macrophage inflammatory protein-3 alpha (MIP-3 alpha) is t he product of recent electronic cloning efforts, however, little characteri zation of its spectrum of biological effects has been undertaken, Human eos inophils exhibited pertussis-toxin-sensitive migration in response to human recombinant (hr)MIP-3 alpha. Messenger RNA for the MIP-3 alpha receptor, C CR-6, and low levels of surface expression were demonstrated by reverse tra nscriptase-polymerase chain reaction and FACS analysis, Analyses of cell si gnaling revealed dose-dependent increases in intracellular calcium mobiliza tion, calciurn transients that were, however, greatly reduced when compared with MCP-3-induced responses, Further investigations of MIP-3 alpha-induce d signal transduction revealed time- and dose-dependent, partially pertussi s toxin-dependent, increases in phosphorylation of the p42/P44 mitogen-acti vated protein kinases (MAPK) that occurred at 10- to 100-fold lower concent rations, and that were linked to a phosphoinositide 3-kinase pathway. These results suggest that MIP-3 alpha can regulate multiple, parallel signal tr ansduction pathways in eosinophils, and suggest that MAPK activation by MIP -3 alpha in eosinophils is a significant signaling pathway for migration in duction.