Biodegradable microspheres containing leukotriene 'B IND.4' and cell-free antigens from Histoplasma capsulatum activate murine bone marrow-derived macrophages
| Autor: | Claudia da Silva Bitencourt, Roberto Nicolete, Patricia R. M. Souza, Guilherme M. Gelfuso, Lúcia Helena Faccioli, Priscilla Aparecida Tartari Pereira, Carlos Arterio Sorgi, Daiane Fernanda dos Santos |
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| Rok vydání: | 2011 |
| Předmět: |
Chemokine
Antigens Fungal Histoplasma Pharmaceutical Science CCL2 Nitric Oxide Leukotriene B4 Microbiology chemistry.chemical_compound Mice Antigen Polylactic Acid-Polyglycolic Acid Copolymer Griess test medicine Zeta potential Animals Lactic Acid Cells Cultured biology Tumor Necrosis Factor-alpha Macrophages In vitro Microspheres PLGA medicine.anatomical_structure chemistry biology.protein Bone marrow Chemokines Polyglycolic Acid LEUCOTRIENOS B |
| Zdroj: | Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP |
| Popis: | Because of the potential protective role of leukotrienes (LTs) in histoplasmosis and the therapeutic and prophylactic effects of cell-free antigens from Histoplasma capsulatum (CFAgs), the aim of this study was to develop and characterise biodegradable LTB4/CFAgs-loaded microspheres (MS) that could promote cellular activation for future immunisation purposes. LTB4/CFAgs-loaded MS that were developed through a double emulsion/extraction process were characterised according to their size, zeta potential, morphology, entrapment efficiency and in vitro release kinetics. We evaluated the uptake of LTB4/CFAgs-loaded MS by bone marrow derived-macrophages (BMDM). The TNF-α and chemokines, and nitrite production, in the supernatant of BMDM cultures were analysed by enzyme-linked immunosorbent assay (ELISA) and Griess reaction, respectively. We found an instantaneous release of CFAgs and a prolonged release of LTB4 from the poly-( d , l -lactide-co-glycolide) (PLGA) MS. The microencapsulation process did not alter the zeta potential nor the spherical morphology of the MS. The appropriate size of the LTB4/CFAgs-loaded MS (smaller than 10 μm) enabled the efficient uptake by BMDM and also induced TNF-α, CXCL1/KC, CCL2/MCP-1, CCL5/RANTES and nitrite oxide release by these cells. In conclusion, the biodegradable LTB4/CFAgs-loaded MS were able to efficiently activate murine BMDM and thereby have the potential to be used in an effective vaccine against H. capsulatum infection. |
| Databáze: | OpenAIRE |
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