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Updated: May 28, 2026
Bone Marrow-derived Macrophage Production
Published on: November 22, 2013
Biodegradable microspheres containing leukotriene B(4) and cell-free antigens from Histoplasma capsulatum activate
Daiane F Dos Santos1, Claudia S Bitencourt, Guilherme M Gelfuso
1Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Universidade de São Paulo, Ribeirão Preto, Brazil.
Abstract:
Because of the potential protective role of leukotrienes (LTs) in histoplasmosis and the therapeutic and prophylactic effects of cell-free antigens from Histoplasmacapsulatum (CFAgs), the aim of this study was to develop and characterise biodegradable LTB(4)/CFAgs-loaded microspheres (MS) that could promote cellular activation for future immunisation purposes. LTB(4)/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 LTB(4)/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 LTB(4) 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 LTB(4)/CFAgs-loaded MS (smaller than 10μm) 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 LTB(4)/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.
Insights
Biodegradable microspheres loaded with leukotriene B4 (LTB4) and Histoplasma capsulatum antigens (CFAgs) effectively activate immune cells. This development shows promise for a new vaccine against Histoplasma capsulatum infection.
Area of Science:
- Immunology
- Biomaterials Science
- Infectious Diseases
Background:
- Leukotrienes (LTs) may protect against histoplasmosis.
- Cell-free antigens from Histoplasma capsulatum (CFAgs) have therapeutic potential.
- Developing effective vaccines against H. capsulatum is crucial.
Purpose of the Study:
- To create and characterize biodegradable microspheres (MS) loaded with LTB4 and CFAgs.
- To assess the ability of these MS to activate immune cells for potential vaccination.
Main Methods:
- Microspheres were fabricated using a double emulsion/extraction process.
- Characterization included size, zeta potential, morphology, and in vitro release kinetics.
- Uptake by bone marrow-derived macrophages (BMDM) and subsequent cytokine/nitrite release were analyzed.
Main Results:
- Microspheres showed immediate CFAg release and prolonged LTB4 release.
- The process maintained MS integrity (size, morphology, zeta potential).
- LTB4/CFAgs-loaded MS were efficiently taken up by BMDM, inducing TNF-α, chemokines, and nitric oxide.
Conclusions:
- Biodegradable LTB4/CFAgs-loaded MS effectively activate murine BMDM.
- These microspheres hold potential for developing a vaccine against H. capsulatum.
