IL-16- and Other CD4 Ligand-Induced Migration Is Dependent upon Protein Kinase C

Human interleukin-16, previously known as lymphocyte chemoattractant factor, is a CD4+T cell competence growth factor initially described as a chemo- tactic factor for CD4+cells. The interaction between IL-16 and its receptor CD4 leads to an increase in intracytoplasmic calcium and inositol trisphosphate. Because of the association of intracellular shifts in protein kinase C (PKC) enzyme activity with production of these secondary messengers and the participation of PKC in transducing certain receptor-mediated migratory signals, we investigated the role of PKC in the CD4-mediated migratory response by IL-16. Recombinant IL-16 induces rapid translocation of PKC from the cytosol to the membrane in three separate CD4+cell types: normal blood T cells, SUPT1 cells, and THP1 cells. PKC inhibitors H7, calphostin C, chelerythrine, and bisindolylmaleimide completely block IL-16-induced lymphocyte migration as well as the motile response induced by HIV-1 gp120 and anti-CD4 antibodies. Taken together, these data suggest a role for PKC in CD4-mediated migratory responses.