Avaliação do efeito da lectina Artin M na expressão de fatores de crescimento e citocinas inflamatórias relacionadas ao processo de repação tecidual: Estudo in vitro em macrófagos e fibroblastos gengivais de ratos

Pós-graduação em Odontologia - FOAR

Influence of Fc gamma RIIIb polymorphism on its ability to cooperate with Fc gamma RIIa and CR3 in mediating the oxidative burst of human neutrophils

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Genotipagem das mutações do gene humano que codifica a lectina ligante da manose de voluntários do Departamento de Parasitologia do Instituto de Biociências

A leishmaniose é uma doença causada pelo protozoário do gênero Leishmania, possuindo uma variedade de formas clínicas. A mais severa é a Leishmaniose visceral, que no Brasil é causada por L. chagasi e transmitida pelo flebotomíneo Lutzomia longipalpis. O cão, tanto o doméstico como o selvagem, é o principal reservatório no ciclo zoonótico da doença, que no Brasil ocorre principalmente na região nordeste. Através de estudos epidemiológicos realizados em áreas endêmicas, notou-se que apesar do elevado número de pessoas infectadas, poucas manifestavam a doença. Isso pode ser explicado pelo estado nutricional e imunológico do paciente, infecção por HIV e variabilidade das cepas, visto que a heterogeneidade genética e diversidade clonal estão relacionadas a variações nos fatores de virulência do parasita. A lectina que se liga à manose (Mannose-Binding Lectin), ou MBL, é uma proteína que pode estar relacionada ao desenvolvimento da doença, uma vez que pode se ligar a carboidratos na membrana externa de patógenos, agindo como uma opsonina e facilitando assim a ação de macrófagos. Altas concentrações desta proteína podem ser desvantajosas, uma vez que pode facilitar a infecção por LV. Genes mutados podem contribuir para a variação do nível sérico da proteína diminuindo as taxas de transcrição do gene. Concluindo, o projeto tem o intuito de identificar e genotipar mutações específicas no promotor e no exon 1 do gene que codifica a MBL em humanos. A realização do estudo permitirá também, a consolidação de uma base de dados para estudos posteriores envolvendo a genética populacional da Lectina Ligante de Manose

Galectin-1 exerts inhibitory effects during DENV-1 infection

Dengue virus (DENV) is an enveloped RNA virus that is mosquito-transmitted and can infect a variety of immune and non-immune cells. Response to infection ranges from asymptomatic disease to a severe disorder known as dengue hemorrhagic fever. Despite efforts to control the disease, there are no effective treatments or vaccines. In our search for new antiviral compounds to combat infection by dengue virus type 1 (DENV-1), we investigated the role of galectin-1, a widely-expressed mammalian lectin with functions in cell-pathogen interactions and immunoregulatory properties. We found that DENV-1 infection of cells in vitro exhibited caused decreased expression of Gal-1 in several different human cell lines, suggesting that loss of Gal-1 is associated with virus production. In test of this hypothesis we found that exogenous addition of human recombinant Gal-1 (hrGal-1) inhibits the virus production in the three different cell types. This inhibitory effect was dependent on hrGal-1 dimerization and required its carbohydrate recognition domain. Importantly, the inhibition was specific for hrGal-1, since no effect was observed using recombinant human galectin-3. Interestingly, we found that hrGal-1 directly binds to dengue virus and acts, at least in part, during the early stages of DENV-1 infection, by inhibiting viral adsorption and its internalization to target cells. To test the in vivo role of Gal-1 in DENV infection, Gal-1-deficient-mice were used to demonstrate that the expression of endogenous Galectin-1 contributes to resistance of macrophages to in vitro-infection with DENV-1 and it is also important to physiological susceptibility of mice to in vivo infection with DENV-1. These results provide novel insights into the functions of Gal-1 in resistance to DENV infection and suggest that Gal-1 should be explored as a potential antiviral compound.

Monocyte migration driven by galectin-3 occurs through distinct mechanisms involving selective interactions with the extracellular matrix

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Immunomodulatory Effects of Galectin-1 on an IgE-Mediated Allergic Conjunctivitis Model

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Galectin-1 exerts inhibitory effects during DENV-1 infection

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Thrombocytopenia and platelet hypoaggregation induced by Bothrops asper snake venom Toxins involved and their contribution to metalloproteinase-induced pulmonary hemorrhage

Thrombocytopenia and platelet dysfunction occur in patients bitten by Bothrops sp snakes in Latin America. An experimental model was developed in mice to study the effects of B. asper venom in platelet numbers and function. Intravenous administration of this venom induces rapid and prominent thrombocytopenia and ex vivo platelet hypoaggregation. The drop in platelet numbers was primarily due to aspercetin, a protein of the C-type lectin family which induces von Willebrand factor-mediated platelet aggregation/agglutination. In addition, the effect of class P-III hemorrhagic metalloproteinases on the microvessel wall also contributes to thrombocytopenia since jararhagin, a P-III metalloproteinase, reduced platelet counts. Hypoaggregation was associated with the action of procoagulant and defibrin(ogen)ating proteinases jararacussin-1 (a thrombin-like serine proteinase) and basparin A (a prothrombin activating metalloproteinase). At the doses which induced hypoaggregation, these enzymes caused defibrin(ogen)ation, increments in fibrin(ogen) degradation products and D-dimer and prolongation of the bleeding time. Incubation of B. asper venom with batimastat and α 2-macroglobulin abrogated the hypoaggregating activity, confirming the role of venom proteinases in this effect. Neither aspercetin nor the defibrin(ogen)ating and hypoaggregating components induced hemorrhage upon intravenous injection. However, aspercetin, but not the thrombin-like or the prothrombin-activating proteinases, potentiated the hemorrhagic activity of two hemorrhagic metalloproteinases in the lungs. © 2005 Schattauer GmbH, Stuttgart.