title: Annexin A1 Is Involved in the Resolution of Inflammatory Responses duringLeishmania braziliensisInfection.
abstract: Leishmaniases are diseases caused by severalLeishmaniaspecies.Leishmania(Viannia)braziliensiscan cause localized cutaneous leishmaniasis (LCL), which heals spontaneously, or mucosal leishmaniasis (ML), characterized by chronic and intense inflammation and scanty parasitism. Annexin A1 (AnxA1) is a protein involved in modulation and resolution of inflammation through multiple mechanisms. In the present study, the role of AnxA1 was investigated inL. braziliensis-infected BALB/c mice. AnxA1 levels increased at the peak of tissue lesion and parasitism in infected mice. AnxA1 increased also afterL. braziliensisinfection of BALB/c (wild-type [WT]) bone marrow derived macrophages. Despite a lower parasite intake, parasite burden in bone marrow-derived macrophages from AnxA1-/-mice was similar to WT and associated with an early increase of TNF-α and, later, of IL-10. AnxA1-/-mice controlled tissue parasitism similarly to WT animals, but they developed significantly larger lesions at later stages of infection, with a more pronounced inflammatory infiltrate and increased specific production of IFN-γ, IL-4, and IL-10. AnxA1-/-mice also presented higher phosphorylation levels of ERK-1/2 and p65/RelA (NF-κB) and inducible NO synthase expression, suggesting that AnxA1 may be involved in modulation of inflammation in this model of experimental leishmaniasis. Finally, assessment of AnxA1 levels in sera from patients with LCL or ML revealed that ML patients had higher levels of serum AnxA1 than did LCL patients or control subjects. Collectively, these data indicate that AnxA1 is actively expressed duringL. braziliensisinfection. In the absence of AnxA1, mice are fully able to control parasite replication, but they present more intense inflammatory responses and delayed ability to resolve their lesion size.
authors.affiliation: Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31270-901, Brazil.
authors.forename: Leandro G
authors.initials: LG
authors.lastname: Oliveira
authors.affiliation: Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31270-901, Brazil.
authors.forename: Míriam C
authors.initials: MC
authors.lastname: Souza-Testasicca
authors.affiliation: Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31270-901, Brazil.|Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31270-901 Brazil.
authors.forename: Juliana P
authors.identifier: 0000-0001-8188-3738
authors.initials: JP
authors.lastname: Vago
authors.affiliation: Laboratório de Imunoparasitologia, Núcleo de Pesquisas em Ciências Biológicas, Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais 35400-000, Brazil.
authors.forename: Amanda Braga
authors.initials: AB
authors.lastname: Figueiredo
authors.affiliation: Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31270-901, Brazil.
authors.forename: Adriana M C
authors.initials: AM
authors.lastname: Canavaci
authors.affiliation: Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31270-901, Brazil.
authors.forename: Luiza Oliveira
authors.initials: LO
authors.lastname: Perucci
authors.affiliation: Laboratório de Inflamação, Instituto Oswaldo Cruz/FIOCRUZ, Rio de Janeiro 21040-360, Brazil.
authors.forename: Tatiana P Teixeira
authors.initials: TP
authors.lastname: Ferreira
authors.affiliation: Programa de Pós-Graduação em Ciências Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31270-901, Brazil; and.
authors.forename: Eduardo A F
authors.initials: EA
authors.lastname: Coelho
authors.affiliation: Programa de Pós-Graduação em Ciências Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31270-901, Brazil; and.
authors.forename: Denise Utsch
authors.initials: DU
authors.lastname: Gonçalves
authors.affiliation: Programa de Pós-Graduação em Ciências Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31270-901, Brazil; and.
authors.forename: Manoel Otávio C
authors.initials: MO
authors.lastname: Rocha
authors.affiliation: Laboratório de Inflamação, Instituto Oswaldo Cruz/FIOCRUZ, Rio de Janeiro 21040-360, Brazil.
authors.forename: Patrícia M R
authors.initials: PM
authors.lastname: E Silva
authors.affiliation: Setor de Patologia Clínica, Colégio Técnico, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31270-901 Brazil.
authors.forename: Cláudia N
authors.initials: CN
authors.lastname: Ferreira
authors.affiliation: Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31270-901 Brazil.
authors.forename: Celso
authors.initials: C
authors.lastname: Queiroz-Junior
authors.affiliation: Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31270-901, Brazil.|Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31270-901 Brazil.
authors.forename: Lirlândia P
authors.initials: LP
authors.lastname: Sousa
authors.affiliation: Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31270-901, Brazil; apfernandes.ufmg@gmail.com.
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Fernandes
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D017305:Annexin A1 / Q000276:immunology*; D015153:Blotting, Western; D002648:Child; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007249:Inflammation / Q000276:immunology; D007892:Leishmania braziliensis; D007896:Leishmaniasis / Q000276:immunology* / Q000473:pathology; D008264:Macrophages / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D055815:Young Adult
chemical_list: D017305:Annexin A1