MIP-3alpha induces human eosinophil migration and activation of the mitogen-activated protein kinases (p42/p44 MAPK).
The CC chemokine macrophage inflammatory protein-3alpha (MIP-3alpha) is the product of recent electronic cloning efforts, however, little characterization of its spectrum of biological effects has been undertaken. Human eosinophils exhibited pertussis-toxin-sensitive migration in response to human recombinant (hr)MIP-3alpha. Messenger RNA for the MIP-3alpha receptor, CCR-6, and low levels of surface expression were demonstrated by reverse transcriptase-polymerase chain reaction and FACS analysis. Analyses of cell signaling revealed dose-dependent increases in intracellular calcium mobilization, calcium transients that were, however, greatly reduced when compared with MCP-3-induced responses. Further investigations of MIP-3alpha-induced signal transduction revealed time- and dose-dependent, partially pertussis toxin-dependent, increases in phosphorylation of the p42/p44 mitogen-activated protein kinases (MAPK) that occurred at 10- to 100-fold lower concentrations, and that were linked to a phosphoinositide 3-kinase pathway. These results suggest that MIP-3alpha can regulate multiple, parallel signal transduction pathways in eosinophils, and suggest that MAPK activation by MIP-3alpha in eosinophils is a significant signaling pathway for migration induction.
Sullivan
S K
SK
Department of Immunology, Neurocrine Biosciences Inc., San Diego, California 92121, USA.
McGrath
D A
DA
Liao
F
F
Boehme
S A
SA
Farber
J M
JM
Bacon
K B
KB
D002118:Calcium / Q000378:metabolism; D002461:Cell Line, Transformed; D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology*; D054418:Chemokine CCL20; D019742:Chemokines, CC / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D004789:Enzyme Activation; D004804:Eosinophils / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology*; D015870:Gene Expression; D006801:Humans; D007424:Intracellular Fluid / Q000378:metabolism; D007457:Iodine Radioisotopes; D019402:Macrophage Inflammatory Proteins; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010766:Phosphorylation; D012333:RNA, Messenger; D054399:Receptors, CCR6; D019707:Receptors, Chemokine / Q000235:genetics; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D014443:Tyrosine / Q000378:metabolism
C108355:CCL20 protein, human; C106311:CCR6 protein, human; D054418:Chemokine CCL20; D019742:Chemokines, CC; D007457:Iodine Radioisotopes; D019402:Macrophage Inflammatory Proteins; D012333:RNA, Messenger; D054399:Receptors, CCR6; D019707:Receptors, Chemokine; D011994:Recombinant Proteins; D014443:Tyrosine; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D002118:Calcium