Professional and non-professional phagocytes: an introduction

Rabinovitch, M.

doi:10.1016/s0962-8924(00)88955-2

Cited by 479 publications

(314 citation statements)

References 26 publications

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“…Although this cell type is rarely discussed as an MPS cell (46,47), our data clearly indicate that granulocytes play a major role in the differential nanoparticle clearance observed between mouse strains. Previous reports indicate that BALB/c mice have greater numbers of circulating granulocytes than C57BL/6 mice (48).…”

Section: Particle Materials and Methodsmentioning

confidence: 63%

Nanoparticle clearance is governed by Th1/Th2 immunity and strain background

Jones¹,

Roberts²,

Robbins³

et al. 2013

J. Clin. Invest.

177

164

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Extended circulation of nanoparticles in blood is essential for most clinical applications. Nanoparticles are rapidly cleared by cells of the mononuclear phagocyte system (MPS). Approaches such as grafting polyethylene glycol onto particles (PEGylation) extend circulation times; however, these particles are still cleared, and the processes involved in this clearance remain poorly understood. Here, we present an intravital microscopybased assay for the quantification of nanoparticle clearance, allowing us to determine the effect of mouse strain and immune system function on particle clearance. We demonstrate that mouse strains that are prone to Th1 immune responses clear nanoparticles at a slower rate than Th2-prone mice. Using depletion strategies, we show that both granulocytes and macrophages participate in the enhanced clearance observed in Th2-prone mice. Macrophages isolated from Th1 strains took up fewer particles in vitro than macrophages from Th2 strains. Treating macrophages from Th1 strains with cytokines to differentiate them into M2 macrophages increased the amount of particle uptake. Conversely, treating macrophages from Th2 strains with cytokines to differentiate them into M1 macrophages decreased their particle uptake. Moreover, these results were confirmed in human monocyte-derived macrophages, suggesting that global immune regulation has a significant impact on nanoparticle clearance in humans. IntroductionThe potential clinical applications of nanoparticles and nanoformulations have been investigated for more than 30 years. Nanoparticle approaches have the potential to revolutionize drug delivery by allowing for the encapsulation of drugs with poor solubility or stability in a stable carrier particle. In addition, targeting nanoparticles to specific pathological sites may allow an increased effective dose of drug at the needed site, while decreasing systemic drug exposure, and therefore side effects. However, to date, only 2 nanoformulations for cancer treatment have been approved for clinical use (liposomal doxorubicin [Doxil] and protein-bound paclitaxel [Abraxane]) (1-3). One major obstacle for the use of nanoparticles in vivo is rapid clearance by the cells of the reticuloendothelial system (RES)/mononuclear phagocyte system (MPS) (4-7). In addition to rapid clearance, variable activity of the MPS among patients leads to widely variable pharmacokinetics of nanoformulations in the clinic, reducing the efficacy of both approved and future experimental nanoformulations (8).

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Section: Particle Materials and Methodsmentioning

confidence: 63%

Nanoparticle clearance is governed by Th1/Th2 immunity and strain background

Jones¹,

Roberts²,

Robbins³

et al. 2013

J. Clin. Invest.

177

164

View full text Add to dashboard Cite

show abstract

“…They both produce a variety of hydrolases [6] which might degrade materials efficiently. As professional and nonprofessional phagocytes, respectively, macrophages and fibroblasts are involved in breaking down of many natural macromolecules [9,10] and could ingest the degraded fragments [6]. In addition, they also produce superoxide anions [11] that could be transformed to more potent oxidants capable of initiating homolytic reactions on polymers [6].…”

Section: Introductionmentioning

confidence: 99%

The biodegradability of electrospun Dextran/PLGA scaffold in a fibroblast/macrophage co-culture

2008

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Fibroblast and macrophage are two dominant cell types respond cooperatively to degrade implanted biomaterials. Using an electrospun Dextran/Poly-lactide-co-glycolide (PLGA) scaffold as a model, an in vitro fibroblast/macrophage co-culture system was developed to investigate the degradability of implantable biodegradable materials. SEM showed that both fibroblasts and macrophages were able to degrade the scaffold, separately or cooperatively. Under the synergistic coordination of macrophages and fibroblasts, scaffolds showed faster degradation rate than their counterparts incubated with a single type of cells as well as in PBS or cell culture medium. Lysozyme, non-specific esterase (NSE), gelatinase, hyaluronidase-1 and α-glucosidase were upregulated in the presence of the scaffold, suggesting their roles in the cell-mediated scaffold degradation. In addition, the expressions of cell surface receptors CD204 and Toll like receptor 4 (TLR4) were elevated one week after cell seeding, implying that these receptors might be involved in scaffold degradation. The results of in vivo subdermal implantation of the scaffold further confirmed the biodegradability of the Dextran/PLGA scaffold. The fibroblast/macrophage co-culture model adequately mimicked the in vivo environment and could be further developed into an in vitro tool for initial biomaterial evaluation.

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“…Because macrophages are professional phagocytes [33], it is important to avoid, or at least to decrease, the degradation of the internalized genetic material by lysosomes. For this purpose, low pH-activated membrane-active peptides [17,18,34] were also associated with the lipid-DNA complexes.…”

Section: Discussionmentioning

confidence: 99%