title: Secretion of multi-protein migratory complex induced by Toxoplasma gondii infection in macrophages involves the uPA/uPAR activation system.
abstract: Toxoplasmosis is a world wide spread zoonosis caused by Toxoplasma gondii, an obligate intracellular parasite that is able to disseminate into deep tissues and cross biological barriers, reaching immunoprivileged sites such as the brain and retina. The parasite is able to infect macrophages and dendritic cells for dispersal throughout the body. However, the molecular mechanisms or outcomes of the subversion of the host cell are largely unknown. Recently our group established that metalloproteinases are involved in migration of infected macrophages. Herein, we evaluated the recruitment of host invasive machinery components in T. gondii infected murine macrophages. We showed by immunoprecipitation assays that MMP-9, CD44 TIMP-1 and uPAR were secreted as a multi-protein complex by infected macrophages. Zymographic analysis revealed that MMP-9 was present in its pro- and active form. Moreover, inhibition of uPA/uPAR pathway by PAI-1 decreased secretion of MMP-9 active forms, as well those associated to uPAR and TIMP-1, but not to CD44. Data presented here suggest that MMP-9 is secreted as a multiprotein complex by T. gondii infected macrophages, similar to that observed in metastatic cells. We further speculate that uPA/uPAR system is involved in the expression/secretion of complexes containing active MMP-9 forms.
authors.affiliation: Laboratório de Biologia do Reconhecer, Centro de Biociências e Biotecnologia, Universidade Estadual do Norte Fluminense, Campos dos Goytacazes, Rio de Janeiro, Brazil.
authors.forename: Sara Hellen Santos
authors.initials: SH
authors.lastname: Schuindt
authors.forename: Bruno Cabral de Lima
authors.initials: BC
authors.lastname: Oliveira
authors.forename: Pollyana Maria de Oliveira
authors.initials: PM
authors.lastname: Pimentel
authors.forename: Thatiane Lacerda
authors.initials: TL
authors.lastname: Resende
authors.forename: Cláudio A
authors.initials: CA
authors.lastname: Retamal
authors.forename: Renato A
authors.initials: RA
authors.lastname: DaMatta
authors.forename: Daniele
authors.initials: D
authors.lastname: Seipel
authors.forename: Andrea Cristina Vetö
authors.initials: AC
authors.lastname: Arnholdt
mesh_terms: D000818:Animals; D002460:Cell Line; D005786:Gene Expression Regulation; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism* / Q000469:parasitology*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000378:metabolism; D055293:Receptors, Urokinase Plasminogen Activator / Q000235:genetics / Q000378:metabolism*; D014122:Toxoplasma / Q000502:physiology*; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics / Q000378:metabolism*
chemical_list: C476399:Cd44 protein, mouse; D018960:Hyaluronan Receptors; D017395:Plasminogen Activator Inhibitor 1; D055293:Receptors, Urokinase Plasminogen Activator; C051321:SERPINE1 protein, human; D014568:Urokinase-Type Plasminogen Activator; D020780:Matrix Metalloproteinase 9