Leishmania mexicana: promastigotes and amastigotes secrete protein phosphatases and this correlates with the production of inflammatory cytokines in macrophages


Por: Escalona-Montano, A. R., Ortiz-Lozano, D. M., Rojas-Bernabe, A., Wilkins-Rodriguez, A. A., Torres-Guerrero, H., Mondragon-Flores, R., Mondragon-Gonzalez, R., Becker, I., Gutierrez-Kobeh, L., Aguirre-Garcia, M. M.

Publicada: 1 sep 2016
Resumen:
Phosphatase activity of Leishmania spp. has been shown to deregulate the signalling pathways of the host cell. We here show that Leishmania mexicana promastigotes and amastigotes secrete proteins with phosphatase activity to the culture medium, which was higher in the Promastigote Secretion Medium (PSM) as compared with the Amastigote Secretion Medium (ASM) and was not due to cell lysis, since parasite viability was not affected by the secretion process. The biochemical characterization showed that the phosphatase activity present in PSM was higher in dephosphorylating the peptide END (pY) INASL as compared with the peptide RRA (pT)VA. In contrast, the phosphatase activity in ASM showed little dephosphorylating capacity for both peptides. Inhibition assays demonstrated that the phosphatase activity of both PSM and ASM was sensible only to protein tyrosine phosphatases inhibitors. An antibody against a protein phosphatase 2C (PP2C) of Leishmania major cross-reacted with a 44.9 kDa molecule in different cellular fractions of L. mexicana promastigotes and amastigotes, however, in PSM and ASM, the antibody recognized a protein about 70 kDa. By electron microscopy, the PP2C was localized in the flagellar pocket of amastigotes. PSM and ASM induced the production of tumor necrosis factor alpha, IL-1 beta, IL-12p70 and IL-10 in human macrophages.

Filiaciones:
Escalona-Montano, A. R.:
 Univ Nacl Autonoma Mexico, Fac Med, Unidad Invest Med Expt, Dr Balmis 148,Colonia Doctores, Mexico City 06726, DF, Mexico

Ortiz-Lozano, D. M.:
 Univ Nacl Autonoma Mexico, Fac Med, Unidad Invest Med Expt, Dr Balmis 148,Colonia Doctores, Mexico City 06726, DF, Mexico

Rojas-Bernabe, A.:
 Univ Nacl Autonoma Mexico, Fac Med, Unidad Invest Med Expt, Dr Balmis 148,Colonia Doctores, Mexico City 06726, DF, Mexico

Wilkins-Rodriguez, A. A.:
 Univ Nacl Autonoma Mexico, Fac Med, Unidad Invest Med Expt, Dr Balmis 148,Colonia Doctores, Mexico City 06726, DF, Mexico

Torres-Guerrero, H.:
 Univ Nacl Autonoma Mexico, Fac Med, Unidad Invest Med Expt, Dr Balmis 148,Colonia Doctores, Mexico City 06726, DF, Mexico

Mondragon-Flores, R.:
 IPN, CINVESTAV, Ctr Invest & Estudios Avanzados, Dept Bioquim, Av Inst Politecn Nacl 2508, Mexico City, DF, Mexico

Mondragon-Gonzalez, R.:
 IPN, CINVESTAV, Ctr Invest & Estudios Avanzados, Dept Genet & Biol Mol, Av Inst Politecn Nacl 2508, Mexico City, DF, Mexico

Becker, I.:
 Univ Nacl Autonoma Mexico, Fac Med, Unidad Invest Med Expt, Dr Balmis 148,Colonia Doctores, Mexico City 06726, DF, Mexico

Gutierrez-Kobeh, L.:
 Univ Nacl Autonoma Mexico, Fac Med, Unidad Invest Med Expt, Dr Balmis 148,Colonia Doctores, Mexico City 06726, DF, Mexico

Aguirre-Garcia, M. M.:
 Univ Nacl Autonoma Mexico, Fac Med, Unidad Invest Med Expt, Dr Balmis 148,Colonia Doctores, Mexico City 06726, DF, Mexico
ISSN: 00311820
Editorial
Cambridge University Press, 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA, Estados Unidos America
Tipo de documento: Article
Volumen: 143 Número: 11
Páginas: 1409-1420
WOS Id: 000381228700007
ID de PubMed: 27220404