title: Insulin-like growth factor-I induces arginase activity in Leishmania amazonensis amastigote-infected macrophages through a cytokine-independent mechanism.
abstract: Leishmania (Leishmania) amazonensis exhibits peculiarities in its interactions with hosts. Because amastigotes are the primary form associated with the progression of infection, we studied the effect of insulin-like growth factor (IGF)-I on interactions between L. (L.) amazonensis amastigotes and macrophages. Upon stimulation of infected macrophages with IGF-I, we observed decreased nitric oxide production but increased arginase expression and activity, which lead to increased parasitism. However, stimulation of amastigote-infected macrophages with IGF-I did not result in altered cytokine levels compared to unstimulated controls. Because IGF-I is present in tissue fluids and also within macrophages, we examined the possible effect of this factor on phosphatidylserine (PS) exposure on amastigotes, seen previously in tissue-derived amastigotes leading to increased parasitism. Stimulation with IGF-I induced PS exposure on amastigotes but not on promastigotes. Using a PS-liposome instead of amastigotes, we observed that the PS-liposome but not the control phosphatidylcholine-liposome led to increased arginase activity in macrophages, and this process was not blocked by anti-TGF-β antibodies. Our results suggest that in L. (L.) amazonensis amastigote-infected macrophages, IGF-I induces arginase activity directly in amastigotes and in macrophages through the induction of PS exposure on amastigotes in the latter, which could lead to the alternative activation of macrophages through cytokine-independent mechanisms.
authors.affiliation: Laboratório de Soroepidemiologia e Imunobiologia, Instituto de Medicina Tropical de São Paulo, Universidade de São Paulo, Avenida Dr. Enéas de Carvalho Aguiar 470, Predio II, 4° Andar, 05403-000 São Paulo, SP, Brazil.
authors.forename: Celia Maria Vieira
authors.initials: CM
authors.lastname: Vendrame
authors.affiliation: Laboratório de Soroepidemiologia e Imunobiologia, Instituto de Medicina Tropical de São Paulo, Universidade de São Paulo, Avenida Dr. Enéas de Carvalho Aguiar 470, Predio II, 4° Andar, 05403-000 São Paulo, SP, Brazil ; Laboratório de Imunofisiopatologia, Instituto de Ciências Biomédicas IV, Universidade de São Paulo, 05508-900 São Paulo, SP, Brazil.
authors.forename: Marcia Dias Teixeira
authors.initials: MD
authors.lastname: Carvalho
authors.affiliation: Departamento de Parasitologia, Instituto Adolfo Lutz, 01246-903 São Paulo, SP, Brazil.
authors.forename: Andre Gustavo
authors.initials: AG
authors.lastname: Tempone
authors.affiliation: Laboratório de Soroepidemiologia e Imunobiologia, Instituto de Medicina Tropical de São Paulo, Universidade de São Paulo, Avenida Dr. Enéas de Carvalho Aguiar 470, Predio II, 4° Andar, 05403-000 São Paulo, SP, Brazil ; Departamento de Medicina Preventiva, Faculdade de Medicina, Universidade de São Paulo, 01246-903 São Paulo, SP, Brazil.
authors.forename: Hiro
authors.identifier: 0000-0001-7048-562X
authors.initials: H
authors.lastname: Goto
mesh_terms: D000818:Animals; D001119:Arginase / Q000378:metabolism*; D015153:Blotting, Western; D016207:Cytokines / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007891:Leishmania / Q000472:pathogenicity*; D008264:Macrophages / Q000201:enzymology* / Q000378:metabolism / Q000469:parasitology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C
chemical_list: D016207:Cytokines; D007334:Insulin-Like Growth Factor I; D001119:Arginase