title: Leishmanial protein kinase C modulates host cell infection via secreted acid phosphatase.
abstract: To study the role of parasite protein kinase C (PKC) activity in the uptake of Leishmania amazonensis by mononuclear phagocytes we treated the parasites with 12-O-tetradecanoyl phorbol-13-acetate (TPA) and/or sphingosine, before interaction assays. Promastigotes of Leishmania amazonensis were incubated with 20 ng/ml TPA and/or 50 ng/ml sphingosine before the interaction with murine peritoneal macrophages. The short treatment enhanced about 200% the parasite association with the host cells, whereas the sphingosine treatment reduced about 50% the promastigote binding, as did the prolonged TPA treatment. The binding of cells treated with both drugs was not significantly altered. Biochemical and cytochemical data indicate that the protein kinase C agonists TPA and sphingosine, respectively, increased and decreased acid phosphatase (AcP) activity. The addition of sodium tartrate, a secreted AcP inhibitor, suppressed the TPA enhancing effects, but did not affect the basal parasite binding observed in control cells. The supernatants of TPA-treated L. amazonensis promastigotes increased the parasite association by about the same extent as the TPA treatment, and this effect was also abolished by tartrate. Although TPA did not enhance the association of L. major, a species that does not secrete AcP, the supernatants of TPA-treated L. amazonensis increased it in a tartrate-sensitive manner. The results suggest that Leishmania amazonensis PKC activity may modulate its interaction with macrophages via secreted AcP.
authors.affiliation: Programa de Parasitologia e Biologia Celular, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Brasil.
authors.forename: M A
authors.initials: MA
authors.lastname: Vannier-Santos
authors.forename: A
authors.initials: A
authors.lastname: Martiny
authors.forename: J R
authors.initials: JR
authors.lastname: Meyer-Fernandes
authors.forename: W
authors.initials: W
authors.lastname: de Souza
mesh_terms: D000135:Acid Phosphatase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D002462:Cell Membrane / Q000201:enzymology; D005407:Flagella / Q000201:enzymology; D006790:Host-Parasite Interactions; D007894:Leishmania mexicana / Q000187:drug effects / Q000201:enzymology / Q000472:pathogenicity*; D017737:Macrophages, Peritoneal / Q000469:parasitology*; D051379:Mice; D011493:Protein Kinase C / Q000819:agonists / Q000378:metabolism*; D013110:Sphingosine / Q000494:pharmacology; D013644:Tartrates / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D013644:Tartrates; D011493:Protein Kinase C; D000135:Acid Phosphatase; D013110:Sphingosine; D013755:Tetradecanoylphorbol Acetate; C029768:tartaric acid