1-Integrins determine the dendritic morphology which enhances DC-SIGN-mediated particle capture by dendritic cells

Andersen, Claire A. Swetman; Handley, Matthew E.; Pollara, Gabriel; Ridley, Anne J.; Katz, David R.; Chain, Benjamin M.

doi:10.1093/intimm/dxl062

Cited by 20 publications

(21 citation statements)

References 22 publications

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“…Nevertheless, the preferential accumulation of DC-SIGN in the leading edge may optimize contact between the dendritic cell and pathogens and/or antigens in sites of infection that enter the DC. Also, the active edges of the dendritic cell lamellipod are known to 'scan' the local environment for efficient particle acquisition (Swetman Andersen et al, 2006); thus, DC-SIGN appears distributed to the active leading edge where it would enhance the antigen-scanning function of the dendritic cell. Little DC-SIGN was observed in the relatively flat ventral membranes of Raji transfectants or within the lamellar membrane of immature dendritic cells.…”

Section: Discussionmentioning

confidence: 99%

Distribution and lateral mobility of DC-SIGN on immature dendritic cells–implications for pathogen uptake

Neumann

Thompson

Jacobson

2008

Journal of Cell Science

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The receptor C-type lectin DC-SIGN (CD209) is expressed by immature dendritic cells, functioning as an antigen capture receptor and cell adhesion molecule. Various microbes, including HIV-1, can exploit binding to DC-SIGN to gain entry to dendritic cells. DC-SIGN forms discrete nanoscale clusters on immature dendritic cells that are thought to be important for viral binding. We confirmed that these DC-SIGN clusters also exist both in live dendritic cells and in cell lines that ectopically express DC-SIGN. Moreover, DC-SIGN has an unusual polarized lateral distribution in the plasma membrane of dendritic cells and other cells: the receptor is preferentially localized to the leading edge of the dendritic cell lamellipod and largely excluded from the ventral plasma membrane. Colocalization of DC-SIGN clusters with endocytic activity demonstrated that surface DC-SIGN clusters are enriched near the leading edge, whereas endocytosis of these clusters occurred preferentially at lamellar sites posterior to the leading edge. Therefore, we predicted that DC-SIGN clusters move from the leading edge to zones of internalization. Two modes of lateral mobility were evident from the trajectories of DC-SIGN clusters at the leading edge, directed and non-directed mobility. Clusters with directed mobility moved in a highly linear fashion from the leading edge to rearward locations in the lamella at remarkably high velocity (1420±260 nm/second). Based on these data, we propose that DC-SIGN clusters move from the leading edge–where the dendritic cell is likely to encounter pathogens in tissue–to a medial lamellar site where clusters enter the cell via endocytosis. Immature dendritic cells may acquire and internalize HIV and other pathogens by this process.

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Section: Discussionmentioning

confidence: 99%

Distribution and lateral mobility of DC-SIGN on immature dendritic cells–implications for pathogen uptake

Neumann

Thompson

Jacobson

2008

Journal of Cell Science

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“…Drugs that inhibit microtubule polymerization, e.g., colchicine, destabilize dendrites and, consequently, prevent particle attachment and capture (Swetman Andersen et al, 2006). For this reason, we tested whether colchicine would inhibit formation of bead-cell complexes.…”

Section: Resultsmentioning

confidence: 99%

Extracellular transport of cell-size particles and tumor cells by dendritic cells in culture

Thacker

Retzinger

Cash

et al. 2013

Experimental and Molecular Pathology

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Many particulate materials of sizes approximating that of a cell disseminate after being introduced into the body. While some move about within phagocytic inflammatory cells, others appear to move about outside of, but in contact with, such cells. In this report, we provide unequivocal photomicroscopic evidence that cultured, mature, human dendritic cells can transportin extracellular fashion over significant distances both polymeric beads and tumor cells. At least in the case of polymeric beads, both fibrinogen and the β2-integrin subunit, CD18, appear to play important roles in the transport process. These discoveries may yield insight into a host of disease-related phenomena, including and especially tumor cell invasion and metastasis.

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“…After coating the nanoparticle surface with these recombinant proteins, we showed that RGDS-PLA nanoparticles were more efficiently taken up by cells harboring α5β1 integrin receptors on their cell surface than uncoated or mutated KGES-coated nanoparticles. As a first approach, a subcutaneous vaccine model was developed to take advantage of the presence of dendritic cells presenting α5β1 integrin receptors on their surface in skin and to a less-extent in subcutaneous tissues, and their potential to migrate to peripheral draining lymph nodes [21–22]. Mice were injected with different types of nanoparticles, coated with p24, an HIV antigen, and with or without RGDS- or KGES-FNIII9/10 recombinant proteins, and the antigenic potential of these formulations was estimated.…”

Section: Introductionmentioning

confidence: 99%

Poly(Lactic Acid) Nanoparticles Targeting α5β1 Integrin as Vaccine Delivery Vehicle, a Prospective Study

et al. 2016

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Biodegradable polymeric nanoparticles are vehicles of choice for drug delivery and have the ability to encapsulate and present at their surface different molecules of interest. Among these bio-nanocarriers, poly(lactic acid) (PLA) nanoparticles have been used as adjuvant and vehicle for enhanced vaccine efficacy. In order to develop an approach to efficient vaccine delivery, we developed nanoparticles to target α5β1 positive cells. We first overproduced, in bacteria, human fibronectin FNIII9/10 recombinant proteins possessing an integrin α5β1 binding site, the RGDS sequence, or a mutated form of this site. After having confirmed the integrin binding properties of these recombinant proteins in cell culture assays, we were able to formulate PLA nanoparticles with these FNIII9/10 proteins at their surface. We then confirmed, by fluorescence and confocal microscopy, an enhanced cellular uptake by α5β1+ cells of RGDS-FNIII9/10 coated PLA nanoparticles, in comparison to KGES-FNIII9/10 coated or non-coated controls. As a first vaccination approach, we prepared PLA nanoparticles co-coated with p24 (an HIV antigen), and RGDS- or KGES-FNIII9/10 proteins, followed by subcutaneous vaccine administration, in mice. Although we did not detect improvements in the apparent humoral response to p24 antigen in the serum of RGDS/p24 nanoparticle-treated mice, the presence of the FNIII proteins increased significantly the avidity index of anti-p24 antibodies compared to p24-nanoparticle-injected control mice. Future developments of this innovative targeted vaccine are discussed.

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1-Integrins determine the dendritic morphology which enhances DC-SIGN-mediated particle capture by dendritic cells

Cited by 20 publications

References 22 publications

Distribution and lateral mobility of DC-SIGN on immature dendritic cells–implications for pathogen uptake

Distribution and lateral mobility of DC-SIGN on immature dendritic cells–implications for pathogen uptake

Extracellular transport of cell-size particles and tumor cells by dendritic cells in culture

Poly(Lactic Acid) Nanoparticles Targeting α5β1 Integrin as Vaccine Delivery Vehicle, a Prospective Study

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