LEISHMANIAL PROTEIN-KINASE-C MODULATES HOST-CELL INFECTION VIA SECRETED ACID-PHOSPHATASE

To study the role of parasite protein kinase C (PKC) activity in the u ptake of Leishmania amazonensis by mononuclear phagocytes we treated t he parasites with 12-O-tetradecanoyl phorbol-13-scetate (TPA) and/or s phingosine, before interaction assays. Promastigotes of Leishmania ama zonensis were incubated with 20 ng/ml TPA and/or 50 ng/ml sphingosine before the interaction with murine peritoneal macrophages. The short t reatment enhanced about 200 % the parasite association with the host c ells, whereas the sphingosine treatment reduced about 50 % the promast igote binding, as did the prolonged TPA treatment. The binding of cell s treated with both drugs was not significantly altered. Biochemical a nd cytochemical data indicate that the protein kinase C agonists TPA a nd sphingosine, respectively, increased and decreased acid phosphatase (AcP) activity The addition of sodium tartrate, a secreted AcP inhibi tor, suppressed the TPA enhancing effects, but did not affect the basa l parasite binding observed in control cells. The supernatants of TPA- treated L. amazonensis promastigotes increased the parasite associatio n by about the same extent as the TPA treatment, and this effect was a lso abolished by tartrate. Although TPA did not enhance the associatio n of L. major, a species that does not secrete AcP, the supernatants o f TPA-treated L. amazonensis increased It in a tartrate-sensitive mann er. The results suggest that Leishmania amazonensis PKC activity may m odulate its interaction with macrophages via secreted AcP.