Insulin-Like Growth Factor-I Induces Arginase Activity in Leishmania amazonensis Amastigote-Infected Macrophages through a Cytokine-Independent Mechanism

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 ma...

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Main Authors: Celia Maria Vieira Vendrame, Marcia Dias Teixeira Carvalho, Andre Gustavo Tempone, Hiro Goto
Format: Article
Language:English
Published: Wiley 2014-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2014/475919
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author Celia Maria Vieira Vendrame
Marcia Dias Teixeira Carvalho
Andre Gustavo Tempone
Hiro Goto
author_facet Celia Maria Vieira Vendrame
Marcia Dias Teixeira Carvalho
Andre Gustavo Tempone
Hiro Goto
author_sort Celia Maria Vieira Vendrame
collection DOAJ
description 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.
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spelling doaj-art-06af0d51db2e4cf08c310429ebb02e162025-08-20T02:03:43ZengWileyMediators of Inflammation0962-93511466-18612014-01-01201410.1155/2014/475919475919Insulin-Like Growth Factor-I Induces Arginase Activity in Leishmania amazonensis Amastigote-Infected Macrophages through a Cytokine-Independent MechanismCelia Maria Vieira Vendrame0Marcia Dias Teixeira Carvalho1Andre Gustavo Tempone2Hiro Goto3Laboratório 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, BrazilLaboratório 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, BrazilDepartamento de Parasitologia, Instituto Adolfo Lutz, 01246-903 São Paulo, SP, BrazilLaboratório 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, BrazilLeishmania (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.http://dx.doi.org/10.1155/2014/475919
spellingShingle Celia Maria Vieira Vendrame
Marcia Dias Teixeira Carvalho
Andre Gustavo Tempone
Hiro Goto
Insulin-Like Growth Factor-I Induces Arginase Activity in Leishmania amazonensis Amastigote-Infected Macrophages through a Cytokine-Independent Mechanism
Mediators of Inflammation
title Insulin-Like Growth Factor-I Induces Arginase Activity in Leishmania amazonensis Amastigote-Infected Macrophages through a Cytokine-Independent Mechanism
title_full Insulin-Like Growth Factor-I Induces Arginase Activity in Leishmania amazonensis Amastigote-Infected Macrophages through a Cytokine-Independent Mechanism
title_fullStr Insulin-Like Growth Factor-I Induces Arginase Activity in Leishmania amazonensis Amastigote-Infected Macrophages through a Cytokine-Independent Mechanism
title_full_unstemmed Insulin-Like Growth Factor-I Induces Arginase Activity in Leishmania amazonensis Amastigote-Infected Macrophages through a Cytokine-Independent Mechanism
title_short Insulin-Like Growth Factor-I Induces Arginase Activity in Leishmania amazonensis Amastigote-Infected Macrophages through a Cytokine-Independent Mechanism
title_sort insulin like growth factor i induces arginase activity in leishmania amazonensis amastigote infected macrophages through a cytokine independent mechanism
url http://dx.doi.org/10.1155/2014/475919
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