Evaluation of particle uptake in human blood monocyte-derived cells in vitro. Does phagocytosis activity of dendritic cells measure up with macrophages?

Thiele, Lars; Rothen‐Rutishauser, Barbara; Jilek, Samantha; Wunderli‐Allenspach, Heidi; Merkle, Hans P.; Walter, Elke

doi:10.1016/s0168-3659(01)00412-6

Cited by 241 publications

(154 citation statements)

References 38 publications

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“…In average, approximately 20 particles/cell were added in these experiments. Thus, based on previous results, phagocytosis is estimated to be about 10 particles/cell for anionic PLA or PLGA microparticles and about 20 particles/cell for cationic microparticles (3,13,27). Anionic and cationic microparticles were loaded with two different types of DNA (Table I).…”

Section: Characterization Of the Various Dna-containing Microparticlementioning

confidence: 79%

“…Microparticles are valuable carriers for the targeting of antigens to APC because they have been demonstrated to be efficiently phagocytosed by DC in vitro (3,13) and in vivo (14). In addition, phagocytosed microparticles release encapsulated antigen into the cells where it is efficiently presented on major histocompatibility complex (MHC) I and MHC II (15).…”

Section: Introductionmentioning

confidence: 99%

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Composition and Surface Charge of DNA-Loaded Microparticles Determine Maturation and Cytokine Secretion in Human Dendritic Cells

Jilek¹,

Ulrich²,

Merkle³

et al. 2004

Pharm Res

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Purpose. Biodegradable microparticles prepared from poly(lactide) (PLA) and poly(lactide-co-glycolide) (PLGA) have been shown to be promising carrier systems for vaccine delivery. Here, we have investigated the capacity of different PLA and PLGA microparticle formulations to induce stimulation of human blood monocyte-derived dendritic cells (DCs). Methods. Stimulation of human derived dendritic cells by plain microparticles were compared with microparticles loaded with plasmid DNA or double-stranded salmon DNA either by encapsulation or adsorption to the surface of cationic microparticles. Stimulation of DCs was monitored by the up-regulation of surface maturation markers CD83 and CD86 and the secretion of IL-12 and TNF-␣. Results. Slowly degrading PLA microparticles did not induce any detectable stimulation or activation of DCs. In contrast, fast degrading PLGA microparticles were able to influence DC maturation and cytokine secretion dependent on their surface charge. Anionic PLGA microparticles induced an up-regulation of CD83 and high TNF-␣ secretion, which was further enhanced up to the level of the potent stimulator lipopolysaccharide (LPS) when plasmid DNA was encapsulated. Moreover, the secretion of significant amounts of IL-12 was observed. Cationic PLGA microparticles induced an up-regulation of CD86 and moderate TNF-␣ secretion, but no IL-12 secretion, with no additional effects in the presence of plasmid DNA. Conclusions. The data suggest that the composition and charge of biodegradable DNA-loaded microparticles profoundly influences maturation and cytokine secretion in DCs. Thus, the individual formulation of microparticles used as a vaccine carrier system might considerably influence the profile of the immune response.

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Section: Characterization Of the Various Dna-containing Microparticlementioning

confidence: 79%

Section: Introductionmentioning

confidence: 99%

Composition and Surface Charge of DNA-Loaded Microparticles Determine Maturation and Cytokine Secretion in Human Dendritic Cells

Jilek¹,

Ulrich²,

Merkle³

et al. 2004

Pharm Res

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“…In other words, DCs can endocytose relatively small particles compared with macrophages (16). Therefore, to enhance DCspecific uptake, it is important to target DCs by using their endocytosis receptor.…”

Section: Resultsmentioning

confidence: 99%

In vivo targeting of dendritic cells for activation of cellular immunity using vaccine carriers based on pH-responsive microparticles

Kwon

James

Shastri

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

192

137

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Activating the immune system to trigger a specific response is a major challenge in vaccine development. In particular, activating sufficient cytotoxic T lymphocyte-mediated cellular immunity, which is crucial for the treatment of many diseases including cancer and AIDS, has proven to be especially challenging. In this study, antigens were encapsulated in acid-degradable polymeric particle carriers to cascade cytotoxic T lymphocyte activation. To target dendritic cells, the most potent antigen-presenting cells, the particle carriers, were further conjugated with monoclonal antibodies. A series of ex vivo and in vivo studies have shown increased receptor-mediated uptake of antibody-conjugated particles by dendritic cells as well as migration of particle-carrying dendritic cells to lymph nodes and stimulation of naïve T cells leading to enhanced cellular immune response as confirmed by specific cell lysis and IFN-␥ secretion.acid-degradable particle ͉ drug delivery ͉ targeted vaccine

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“…MDDCs were treated with PVA-SPIONs (10 and 20 mg/ml) during 4 h and subsequently incubated with Transferrin Alexa 633 (100 mg/ml; marker for lysosomes) for 20 min either in the absence or presence of cytochalasin D (Cyt-D; 10 mg/ml) added to the cell cultures 30 min before particle exposure as previously described (Thiele et al 2001). Cells were fixed in 2.5% glutaraldehyde and processed for TEM (see below).…”

Section: Quantification Of Endocytosed Spions and Co-localization By mentioning

confidence: 99%

Biomedical nanoparticles modulate specific CD4⁺T cell stimulation by inhibition of antigen processing in dendritic cells

et al. 2011

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Understanding how nanoparticles may affect immune responses is an essential prerequisite to developing novel clinical applications. To investigate nanoparticle-dependent outcomes on immune responses, dendritic cells (DCs) were treated with model biomedical poly(vinylalcohol)-coated super-paramagnetic iron oxide nanoparticles (PVA-SPIONs). PVA-SPIONs uptake by human monocyte-derived DCs (MDDCs) was analyzed by flow cytometry (FACS) and advanced imaging techniques. Viability, activation, function, and stimulatory capacity of MDDCs were assessed by FACS and an in vitro CD4 + T cell assay. PVA-SPION uptake was dose-dependent, decreased by lipopolysaccharide (LPS)-induced MDDC maturation at higher particle concentrations, and was inhibited by cytochalasin D pre-treatment. PVA-SPIONs did not alter surface marker expression (CD80, CD83, CD86, myeloid/plasmacytoid DC markers) or antigen-uptake, but decreased the capacity of MDDCs to process antigen, stimulate CD4 + T cells, and induce cytokines. The decreased antigen processing and CD4 + T cell stimulation capability of MDDCs following PVA-SPION treatment suggests that MDDCs may revert to a more functionally immature state following particle exposure.

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Evaluation of particle uptake in human blood monocyte-derived cells in vitro. Does phagocytosis activity of dendritic cells measure up with macrophages?

Cited by 241 publications

References 38 publications

Composition and Surface Charge of DNA-Loaded Microparticles Determine Maturation and Cytokine Secretion in Human Dendritic Cells

Composition and Surface Charge of DNA-Loaded Microparticles Determine Maturation and Cytokine Secretion in Human Dendritic Cells

In vivo targeting of dendritic cells for activation of cellular immunity using vaccine carriers based on pH-responsive microparticles

Biomedical nanoparticles modulate specific CD4⁺T cell stimulation by inhibition of antigen processing in dendritic cells

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Evaluation of particle uptake in human blood monocyte-derived cells in vitro. Does phagocytosis activity of dendritic cells measure up with macrophages?

Cited by 241 publications

References 38 publications

Composition and Surface Charge of DNA-Loaded Microparticles Determine Maturation and Cytokine Secretion in Human Dendritic Cells

Composition and Surface Charge of DNA-Loaded Microparticles Determine Maturation and Cytokine Secretion in Human Dendritic Cells

In vivo targeting of dendritic cells for activation of cellular immunity using vaccine carriers based on pH-responsive microparticles

Biomedical nanoparticles modulate specific CD4+T cell stimulation by inhibition of antigen processing in dendritic cells

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Product

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Biomedical nanoparticles modulate specific CD4⁺T cell stimulation by inhibition of antigen processing in dendritic cells