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Macropinocytosis

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https://www.readbyqxmd.com/read/28109445/identification-of-novel-macropinocytosing-human-antibodies-by-phage-display-and-high-content-analysis
#1
K D Ha, S M Bidlingmaier, Y Su, N-K Lee, B Liu
Internalizing antibodies have great potential for the development of targeted therapeutics. Antibodies that internalize via the macropinocytosis pathway are particularly promising since macropinocytosis is capable of mediating rapid, bulk uptake and is selectively upregulated in many cancers. We hereby describe a method for identifying antibodies that internalize via macropinocytosis by screening phage-displayed single-chain antibody selection outputs with an automated fluorescent microscopy-based high-content analysis platform...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28108630/macropinocytosis-of-nab-paclitaxel-drives-macrophage-activation-in-pancreatic-cancer
#2
Jane E Cullis, Despina Siolas, Antonina Avanzi, Sugata Barui, Anirban Maitra, Dafna Bar-Sagi
Pancreatic cancer is a devastating disease that is largely refractory to currently available treatment strategies. Therapeutic resistance is partially attributed to the dense stromal reaction of PDAC tumors that includes a pervasive infiltration of immunosuppressive (M2) macrophages. Nab-paclitaxel (trade name Abraxane) is a nanoparticle albumin-bound formulation of paclitaxel that, in combination with gemcitabine, is currently the first line treatment for pancreatic cancer. Here, we show that macrophages internalized nab-paclitaxel via macropinocytosis...
January 20, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28107195/a-new-hdac-inhibitor-cinnamoylphenazine-shows-antitumor-activity-in-association-with-intensive-macropinocytosis
#3
Bing-Yan Zhu, Bo-Yang Shang, Yue Du, Yi Li, Liang Li, Xian-Dong Xu, Yong-Su Zhen
Previous studies have shown that intensive macropinocytosis occurs in cancer cells and neutral red (NR) is noted for its capability to enter into the cell massively through a process mimetic to macropinocytosis. In addition, trans-cinnamic acid (tCA) has been found to be an inhibitor of histone deacetylase (HDAC). In the present study, cinnamoylphenazine (CA-PZ) that consists of NR and tCA moieties was synthesized and evaluated. As shown, CA-PZ massively entered into colon carcinoma HT-29 cells and pancreatic carcinoma MIA PaCa-2 cells and this entry was blocked by 5-(N-ethyl-N-isopropyl) amiloride (EIPA, an inhibitor of macropinocytosis), indicating a macropinocytosis-mediated uptake...
January 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28100610/the-measles-virus-receptor-slamf1-can-mediate-particle-endocytosis
#4
Daniel Gonçalves-Carneiro, Jane A McKeating, Dalan Bailey
: The signalling lymphocyte activation molecule F1 (SLAMF1) is both a microbial sensor and entry receptor for Measles virus (MeV). Herein, we describe a new role for SLAMF1 to mediate MeV endocytosis that is in contrast with the alternative, and generally accepted, model that MeV genome enters cells only after fusion at the cell surface. We demonstrated that MeV engagement of SLAMF1 induces dramatic but transient morphological changes, most prominently in the formation of membrane blebs, which were shown to co-localise with incoming viral particles, and rearrangement of the actin cytoskeleton in infected cells...
January 18, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28087571/pancreatic-tumors-exhibit-enhanced-extracellular-protein-catabolism
#5
(no author information available yet)
PDACs gain necessary amino acids via macropinocytosis and degradation of extracellular proteins.
January 13, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28078484/the-effect-of-surface-charges-on-the-cellular-uptake-of-liposomes-investigated-by-live-cell-imaging
#6
Ji Hee Kang, Woo Young Jang, Young Tag Ko
PURPOSE: Liposomes have been developed as versatile nanocarriers for various pharmacological agents. The effect of surface charges on the cellular uptake of the liposomes has been studied by various methods using mainly fixed cells with inevitable limitations. Live cell imaging has been proposed as an alternative methods to overcome the limitations of the fixed cell-based analysis. In this study, we aimed to investigate the effects of surface charges on cellular association and internalization of the liposomes using live cell imaging...
January 11, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28049146/dissecting-bacterial-cell-wall-entry-and-signaling-in-eukaryotic-cells-an-actin-dependent-pathway-parallels-platelet-activating-factor-receptor-mediated-endocytosis
#7
Lip Nam Loh, Geli Gao, Elaine I Tuomanen
: The Gram-positive bacterial cell wall (CW) peptidoglycan-teichoic acid complex is released into the host environment during bacterial metabolism or death. It is a highly inflammatory Toll-like receptor 2 (TLR2) ligand, and previous in vivo studies have demonstrated its ability to recapitulate pathological features of pneumonia and meningitis. We report that an actin-dependent pathway is involved in the internalization of the CW by epithelial and endothelial cells, in addition to the previously described platelet-activating factor receptor (PAFr)-dependent uptake pathway...
January 3, 2017: MBio
https://www.readbyqxmd.com/read/28043524/in-vitro-effects-of-water-pipe-smoke-condensate-on-the-endocytic-activity-of-type-ii-alveolar-epithelial-cells-a549-with-bacillus-calmette-gu%C3%A3-rin
#8
Ian M Adcock, Esmaeil Mortaz, Shamila D Alipoor, Johan Garssen, Ali Akbar Velayati
OBJECTIVE/BACKGROUND: Tuberculosis (TB) is a major global health problem and poses immense threats to many populations. The association between tobacco smoke and TB has already been studied. Water-pipe smoking has become an increasing problem not only in Middle Eastern countries but also globally as it is considered by users as being safer than cigarettes. The presence of high levels of toxic substances in water-pipe smoke may be predisposing factors that enhance the incidence of pulmonary disorders in water-pipe smokers...
December 2016: International Journal of Mycobacteriology
https://www.readbyqxmd.com/read/28036370/fc%C3%AE-receptor-iia-mediated-src-signaling-pathway-is-essential-for-the-antibody-dependent-enhancement-of-ebola-virus-infection
#9
Wakako Furuyama, Andrea Marzi, Aaron B Carmody, Junki Maruyama, Makoto Kuroda, Hiroko Miyamoto, Asuka Nanbo, Rashid Manzoor, Reiko Yoshida, Manabu Igarashi, Heinz Feldmann, Ayato Takada
Antibody-dependent enhancement (ADE) of Ebola virus (EBOV) infection has been demonstrated in vitro, raising concerns about the detrimental potential of some anti-EBOV antibodies. ADE has been described for many viruses and mostly depends on the cross-linking of virus-antibody complexes to cell surface Fc receptors, leading to enhanced infection. However, little is known about the molecular mechanisms underlying this phenomenon. Here we show that Fcγ-receptor IIa (FcγRIIa)-mediated intracellular signaling through Src family protein tyrosine kinases (PTKs) is required for ADE of EBOV infection...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/28032534/improved-oral-bioavailability-and-therapeutic-efficacy-of-dabigatran-etexilate-via-soluplus-%C3%A2-tpgs-binary-mixed-micelles-system
#10
Mei Hu, Jinjie Zhang, Rui Ding, Yao Fu, Tao Gong, Zhirong Zhang
The clinical use of dabigatran etexilate (DABE) is limited by its poor absorption and relatively low bioavailability. Our study aimed to explore the potential of a mixed micelle system composed of Soluplus(®) and D-alpha tocopheryl polyethylene glycol 1000 succinate (TPGS) to improve the oral absorption and bioavailability of DBAE. DBAE was first encapsulated into Soluplus/TPGS mixed micelles by a simple thin film hydration method. The DBAE loaded micelles displayed an average size distribution of around 83...
December 29, 2016: Drug Development and Industrial Pharmacy
https://www.readbyqxmd.com/read/28027923/specific-uptake-mechanisms-of-well-tolerated-thermoresponsive-polyglycerol-based-nanogels-in-antigen-presenting-cells-of-the-skin
#11
Alexander Edlich, Christian Gerecke, Michael Giulbudagian, Falko Neumann, Sarah Hedtrich, Monika Schäfer-Korting, Nan Ma, Marcelo Calderon, Burkhard Kleuser
Engineered nanogels are of high value for a targeted and controlled transport of compounds due to the ability to change their chemical properties by external stimuli. As it has been indicated that nanogels possess a high ability to penetrate the stratum corneum, it cannot be excluded that nanogels interact with dermal dendritic cells, especially in diseased skin. In this study the potential crosstalk of the thermoresponsive nanogels (tNGs) with the dendritic cells of the skin was investigated with the aim to determine the immunotoxicological properties of the nanogels...
December 24, 2016: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28024915/how-do-megakaryocytic-microparticles-target-and-deliver-cargo-to-alter-the-fate-of-hematopoietic-stem-cells
#12
Jinlin Jiang, Chen-Yuan Kao, Eleftherios T Papoutsakis
Megakaryocytic microparticles (MkMPs), the most abundant MPs in circulation, can induce the differentiation of hematopoietic stem and progenitor cells (HSPCs) into functional megakaryocytes. This MkMP capability could be explored for applications in transfusion medicine but also for delivery of nucleic acids and other molecules to HSPCs for targeted molecular therapy. Understanding how MkMPs target, deliver cargo and alter the fate of HSPCs is important for exploring such applications. We show that MkMPs, which are distinct from Mk exosomes (MkExos), target HSPCs with high specificity since they have no effect on other ontologically or physiologically related cells, namely mesenchymal stem cells, endothelial cells or granulocytes...
December 24, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28024083/direct-evidence-for-cancer-cell-autonomous-extracellular-protein-catabolism-in-pancreatic-tumors
#13
Shawn M Davidson, Oliver Jonas, Mark A Keibler, Han Wei Hou, Alba Luengo, Jared R Mayers, Jeffrey Wyckoff, Amanda M Del Rosario, Matthew Whitman, Christopher R Chin, Kendall J Condon, Alex Lammers, Katherine A Kellersberger, Brian K Stall, Gregory Stephanopoulos, Dafna Bar-Sagi, Jongyoon Han, Joshua D Rabinowitz, Michael J Cima, Robert Langer, Matthew G Vander Heiden
Mammalian tissues rely on a variety of nutrients to support their physiological functions. It is known that altered metabolism is involved in the pathogenesis of cancer, but which nutrients support the inappropriate growth of intact malignant tumors is incompletely understood. Amino acids are essential nutrients for many cancer cells that can be obtained through the scavenging and catabolism of extracellular protein via macropinocytosis. In particular, macropinocytosis can be a nutrient source for pancreatic cancer cells, but it is not fully understood how the tumor environment influences metabolic phenotypes and whether macropinocytosis supports the maintenance of amino acid levels within pancreatic tumors...
December 26, 2016: Nature Medicine
https://www.readbyqxmd.com/read/28007579/g-quadruplex-oligonucleotide-as1411-as-a-cancer-targeting-agent-uses-and-mechanisms
#14
REVIEW
Paula J Bates, Elsa M Reyes-Reyes, Mohammad T Malik, Emily M Murphy, Martin G O'Toole, John O Trent
BACKGROUND: AS1411 is a 26-mer G-rich DNA oligonucleotide that forms a variety of G-quadruplex structures. It was identified based on its cancer-selective antiproliferative activity and subsequently determined to be an aptamer to nucleolin, a multifunctional protein that preferentially binds quadruplex nucleic acids and which is present at high levels on the surface of cancer cells. AS1411 has exceptionally efficient cellular internalization compared to non-quadruplex DNA sequences. SCOPE OF REVIEW: Recent developments related to AS1411 will be examined, with a focus on its use for targeted delivery of therapeutic and imaging agents...
December 20, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27992192/heparin-enhances-transfection-in-concert-with-a-trehalose-based-polycation-with-challenging-cell-types
#15
William S Boyle, Kyle Senger, Jakub Tolar, Theresa M Reineke
Improving the delivery of nucleic acids to diverse tissue types in culture is important for translating genome editing for regenerative cell therapies. Herein, we examine the effect of transfection media additives, such as the sulfated glycosaminoglycan heparin, in dramatically increasing pDNA delivery efficiency and transgene expression in a wide variety of cell types. Polyplexes formed by combining pDNA and Tr4, a cationic glycopolymer containing repeated trehalose and pentaethylenetetramine groups, were treated with low concentrations of heparin prior to in vitro transfection with plasmid DNA...
December 19, 2016: Biomacromolecules
https://www.readbyqxmd.com/read/27974557/african-swine-fever-virus-gets-undressed-new-insights-on-the-entry-pathway
#16
Germán Andrés
African swine fever virus (ASFV) is a large multienveloped DNA virus composed of a genome-containing core successively wrapped by an inner lipid envelope, an icosahedral protein capsid and an outer lipid envelope. In keeping with this structural complexity, recent studies have revealed an intricate entry program. This Gem article highlights how ASFV uses two alternative pathways, macropinocytosis and clathrin-mediated endocytosis, to enter into the host macrophage and how the endocytosed particles undergo a stepwise, low pH-driven disassembly leading to inner envelope fusion and core delivery in the cytoplasm...
December 14, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27960076/a-plasma-membrane-template-for-macropinocytic-cups
#17
Douwe M Veltman, Thomas D Williams, Gareth Bloomfield, Bi-Chang Chen, Eric Betzig, Robert H Insall, Robert R Kay
Macropinocytosis is a fundamental mechanism that allows cells to take up extracellular liquid into large vesicles. It critically depends on the formation of a ring of protrusive actin beneath the plasma membrane, which develops into the macropinocytic cup. We show that macropinocytic cups in Dictyostelium are organised around coincident intense patches of PIP3, active Ras and active Rac. These signalling patches are invariably associated with a ring of active SCAR/WAVE at their periphery, as are all examined structures based on PIP3 patches, including phagocytic cups and basal waves...
December 13, 2016: ELife
https://www.readbyqxmd.com/read/27958762/cd47-and-nox1-mediate-dynamic-fluid-phase-macropinocytosis-of-native-ldl
#18
Gabor Csanyi, Douglas M Feck, Pushpankur Ghoshal, Bhupesh Singla, Hui-Ping Lin, Shanmugam Nagarajan, Daniel N Meijles, Imad Al Ghouleh, Nadiezhda Cantu-Medellin Cantu-Medellin, Eric E Kelley, Lukasz Mateuszuk Mateuszuk, Jeffrey S Isenberg, Simon C Watkins, Patrick J Pagano
AIMS: Macropinocytosis has been implicated in cardiovascular and other disorders yet the physiological factors that initiate fluid-phase internalization and the signaling mechanisms involved remain poorly identified. The present study was designed to examine whether matrix protein thrombospondin-1 (TSP1) stimulates macrophage macropinocytosis and, if so, to investigate the potential signaling mechanism involved. RESULTS: TSP1 treatment of human and murine macrophages stimulated membrane ruffle formation and pericellular solute internalization by macropinocytosis...
December 13, 2016: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/27936565/heparin-promoted-cellular-uptake-of-the-cell-penetrating-glycosaminoglycan-binding-peptide-gbpecp-depends-on-a-single-tryptophan
#19
Li-Chun Hung, Ingjye Jiang, Chien-Jung Chen, Jia-Yin Lu, Yi-Fen Hsieh, Ping-Hsieh Kuo, Yi-Lin Hung, Lily Hui-Ching Wang, Margaret Dah-Tsyr Chang, Shih-Che Sue
A 10-residue, glycosaminoglycan-binding peptide, GBPECP, derived from human eosinophil cationic protein has been recently designated as a potent cell-penetrating peptide. A model system containing peptide, glycan, and lipid was monitored by nuclear magnetic resonance (NMR) spectroscopy to determine the cell-penetrating mechanism. Heparin octasaccharide with dodecylphosphocholine (DPC) lipid micelle was titrated into the GBPECP solution. Our data revealed substantial roles for the charged residues Arg5 and Lys7 in recognizing heparin, whereas Arg3 had less effect...
December 21, 2016: ACS Chemical Biology
https://www.readbyqxmd.com/read/27909711/effect-of-partial-pegylation-on-particle-uptake-by-macrophages
#20
Lucero Sanchez, Yi Yi, Yan Yu
Controlling the internalization of synthetic particles by immune cells remains a grand challenge for developing successful drug carrier systems. Polyethylene glycol (PEG) is frequently used as a protective coating on particles to evade immune clearance, but it also hinders the interactions of particles with their intended target cells. In this study, we investigate a spatial decoupling strategy, in which PEGs are coated on only one hemisphere of particles, so that the other hemisphere is available for functionalization of cell-targeting ligands without the hindrance effect from the PEGs...
January 7, 2017: Nanoscale
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