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Nature Reviews. Molecular Cell Biology Aug 2008The ingestion of particles or cells by phagocytosis and of fluids by macropinocytosis requires the formation of large endocytic vacuolar compartments inside cells by the... (Review)
Review
The ingestion of particles or cells by phagocytosis and of fluids by macropinocytosis requires the formation of large endocytic vacuolar compartments inside cells by the organized movements of membranes and the actin cytoskeleton. Fc-receptor-mediated phagocytosis is guided by the zipper-like progression of local, receptor-initiated responses that conform to particle geometry. By contrast, macropinosomes and some phagosomes form with little or no guidance from receptors. The common organizing structure is a cup-shaped invagination of the plasma membrane that becomes the phagosome or macropinosome. Recent studies, focusing on the physical properties of forming cups, indicate that a feedback mechanism regulates the signal transduction of phagocytosis and macropinocytosis.
Topics: Animals; Cell Physiological Phenomena; Cell Shape; Feedback, Physiological; Humans; Models, Biological; Phagocytosis; Phagosomes; Pinocytosis; Signal Transduction
PubMed: 18612320
DOI: 10.1038/nrm2447 -
Philosophical Transactions of the Royal... Feb 2019Macrophages respond to several stimuli by forming florid membrane ruffles that lead to fluid uptake by macropinocytosis. This type of induced macropinocytosis, executed... (Review)
Review
Macrophages respond to several stimuli by forming florid membrane ruffles that lead to fluid uptake by macropinocytosis. This type of induced macropinocytosis, executed by a variety of non-malignant and malignant cells, is initiated by transmembrane receptors and is involved in nutrient acquisition and mTOR signalling. However, macrophages also perform a unique type of constitutive ruffling and macropinocytosis that is dependent on the presence of extracellular calcium. Calcium-sensing receptors are responsible for this activity. This distinct form of macropinocytosis enables macrophages to continuously sample their microenvironment for antigenic molecules and for pathogen- and danger-associated molecular patterns, as part of their immune surveillance functions. Interestingly, even within the monocyte lineage, there are differences in macropinocytic ability that reflect the polarized functional roles of distinct macrophage subsets. This review discusses the shared and distinct features of both induced and constitutive macropinocytosis displayed by the macrophage lineage and their roles in physiology, immunity and pathophysiology. In particular, we analyse the role of macropinocytosis in the uptake of modified low-density lipoprotein (LDL) and its contribution to foam cell and atherosclerotic plaque formation. We propose a combined role of scavenger receptors and constitutive macropinocytosis in oxidized LDL uptake, a process we have termed 'receptor-assisted macropinocytosis'. This article is part of the Theo Murphy meeting issue 'Macropinocytosis'.
Topics: Animals; Atherosclerosis; Humans; Immunity; Macrophages; Pinocytosis
PubMed: 30967001
DOI: 10.1098/rstb.2018.0147 -
Journal of Nanoscience and... Dec 2010Quantum dots (QDs) are luminescent semiconductor nanocrystals that are widely used as fluorescent probes in biomedical applications, including cellular imaging and tumor... (Review)
Review
Quantum dots (QDs) are luminescent semiconductor nanocrystals that are widely used as fluorescent probes in biomedical applications, including cellular imaging and tumor tracking. Cell-penetrating peptides (CPPs), also called protein transduction domains (PTDs), are short basic peptides that permeate cell membranes and are able to deliver a variety of macromolecule cargoes, such as DNAs, RNAs, proteins, and nanomaterials. Here we review strategies to couple QDs to CPPs, by either covalent linkages or noncovalent interactions, to provide a tool to study intracellular delivery. This facilitated transport of QDs by CPPs into cells is both simple and efficient. Accordingly, CPP-QD nanoparticles are likely to be of broad utility in biological research and advance the development of medical and pharmaceutical therapeutics.
Topics: Cell-Penetrating Peptides; Drug Delivery Systems; Nanocomposites; Pinocytosis; Protein Transport; Quantum Dots
PubMed: 21121277
DOI: 10.1166/jnn.2010.3012 -
Scientific Reports Jan 2021Neutrophil activation is an integral process to acute inflammation and is associated with adverse clinical sequelae. Identification of neutrophil activation in real time... (Clinical Trial)
Clinical Trial
Neutrophil activation is an integral process to acute inflammation and is associated with adverse clinical sequelae. Identification of neutrophil activation in real time in the lungs of patients may permit biological stratification of patients in otherwise heterogenous cohorts typically defined by clinical criteria. No methods for identifying neutrophil activation in real time in the lungs of patients currently exist. We developed a bespoke molecular imaging probe targeting three characteristic signatures of neutrophil activation: pinocytosis, phagosomal alkalinisation, and human neutrophil elastase (HNE) activity. The probe functioned as designed in vitro and ex vivo. We evaluated optical endomicroscopy imaging of neutrophil activity using the probe in real-time at the bedside of healthy volunteers, patients with bronchiectasis, and critically unwell mechanically ventilated patients. We detected a range of imaging responses in vivo reflecting heterogeneity of condition and severity. We corroborated optical signal was due to probe function and neutrophil activation.
Topics: Animals; Bronchiectasis; Humans; Inflammation; Lung; Male; Neutrophil Activation; Neutrophils; Pancreatic Elastase; Pinocytosis; Spectrometry, Fluorescence
PubMed: 33441792
DOI: 10.1038/s41598-020-80083-w -
Traffic (Copenhagen, Denmark) Dec 2018Macropinosomes, phagosomes and autolysosomes are comparatively large, quasi-spherical organelles that play essential functions in immunity and homeostasis. These... (Review)
Review
Macropinosomes, phagosomes and autolysosomes are comparatively large, quasi-spherical organelles that play essential functions in immunity and homeostasis. These vacuolar organelles are relatively short-lived, promptly fragmenting into smaller structures. Vacuolar resolution is mediated by tubulation and vesiculation, processes orchestrated by protein complexes that are recruited to highly curved membranes. Importantly, the surface-to-volume ratios of the tubules and vesicles generated during the resolution process are considerably larger than that of the parental vacuole. Because membranes under high hydrostatic tension resist deformation, an active, concomitant loss of volume is required to sustain the resolution process and may even initiate tubulation and vesiculation. Despite its fundamental role in membrane remodeling, the mechanisms that account for organellar volume loss are poorly understood, but are likely to involve the export of solutes followed by osmotically obliged water. In this review, we describe the principles and possible mechanisms underlying the resolution of organelles, with particular attention paid to the osmolytes they contain and the pathways mediating their exit.
Topics: Animals; Cytoplasmic Vesicles; Humans; Microtubules; Osmotic Pressure; Phagocytosis; Pinocytosis
PubMed: 30159984
DOI: 10.1111/tra.12614 -
Traffic (Copenhagen, Denmark) May 2001Phagocytosis and macropinocytosis are actin-dependent clathrin-independent processes primarily performed by cells like neutrophils and macrophages that result in the... (Review)
Review
Phagocytosis and macropinocytosis are actin-dependent clathrin-independent processes primarily performed by cells like neutrophils and macrophages that result in the internalization of particles or the formation of fluid-filled macropinosomes, respectively. Phagocytosis consists of a number of stages, including attachment of particles to cell surface receptors, engulfment of the particle dependent on actin polymerization and membrane exocytosis, and formation of phago-lysosomes. In contrast, the molecular steps regulating macropinocytosis are only just now being deciphered. Much remains to be learned concerning the signaling pathways that regulate these processes. Dictyostelium is a genetically and biochemically tractable professional phagocyte that has proven to be a powerful system with which to determine the nature of the molecular steps involved in regulating these internalization processes. This review summarizes what is currently understood concerning the molecular mechanisms governing phagocytosis and macropinocytosis in Dictyostelium and describes recent data concerning the common and distinct pathways that regulate these processes.
Topics: Animals; Dictyostelium; Phagocytosis; Phosphatidylinositols; Pinocytosis
PubMed: 11350627
DOI: 10.1034/j.1600-0854.2001.002005311.x -
Frontiers in Immunology 2018Macropinocytosis has received increasing attention in recent years for its various roles in nutrient acquisition, immune surveillance, and virus and cancer pathologies.... (Review)
Review
Macropinocytosis has received increasing attention in recent years for its various roles in nutrient acquisition, immune surveillance, and virus and cancer pathologies. In most cases macropinocytosis is initiated by the sudden increase in an external stimulus such as a growth factor. This "induced" form of macropinocytosis has been the subject of much of the work addressing its mechanism and function over the years. An alternative, "constitutive" form of macropinocytosis restricted to primary innate immune cells also exists, although its mechanism has remained severely understudied. This mini-review focuses on the very recent advances that have shed new light on the initiation, formation and functional relevance of constitutive macropinocytosis in primary innate immune cells. An emphasis is placed on how this new understanding of constitutive macropinocytosis is helping to define the sentinel function of innate immune cells including polarized macrophages and dendritic cells.
Topics: Animals; Antigen Presentation; Biomarkers; Dendritic Cells; Humans; Immunity, Innate; Immunologic Surveillance; Macrophages; Pinocytosis; Receptors, Pattern Recognition; Signal Transduction
PubMed: 30333835
DOI: 10.3389/fimmu.2018.02286 -
International Journal of Molecular... Nov 2020Pancreatic ductal adenocarcinoma (PDAC), an extremely aggressive invasive cancer, is the fourth most common cause of cancer-related death in the United States. The... (Review)
Review
Pancreatic ductal adenocarcinoma (PDAC), an extremely aggressive invasive cancer, is the fourth most common cause of cancer-related death in the United States. The higher mortality in PDAC is often attributed to the inability to detect it until it has reached advanced stages. The major challenge in tackling PDAC is due to its elusive pathology, minimal effectiveness, and resistance to existing therapeutics. The aggressiveness of PDAC is due to the capacity of tumor cells to alter their metabolism, utilize the diverse available fuel sources to adapt and grow in a hypoxic and harsh environment. Therapeutic resistance is due to the presence of thick stroma with poor angiogenesis, thus making drug delivery to tumor cells difficult. Investigating the metabolic mediators and enzymes involved in metabolic reprogramming may lead to the identification of novel therapeutic targets. The metabolic mediators of glucose, glutamine, lipids, nucleotides, amino acids and mitochondrial metabolism have emerged as novel therapeutic targets. Additionally, the role of autophagy, macropinocytosis, lysosomal transport, recycling, amino acid transport, lipid transport, and the role of reactive oxygen species has also been discussed. The role of various pro-inflammatory cytokines and immune cells in the pathogenesis of PDAC and the metabolites involved in the signaling pathways as therapeutic targets have been previously discussed. This review focuses on the therapeutic potential of metabolic mediators in PDAC along with stemness due to metabolic alterations and their therapeutic importance.
Topics: Adenocarcinoma; Amino Acids; Animals; Autophagy; Carcinoma, Pancreatic Ductal; Cytokines; Humans; Pancreatic Neoplasms; Pinocytosis; Reactive Oxygen Species; Signal Transduction
PubMed: 33198082
DOI: 10.3390/ijms21228502 -
Histochemistry and Cell Biology Mar 2008Today it is generally accepted that there are several endocytic mechanisms, both the clathrin-dependent one and mechanisms which operate without clathrin and with... (Review)
Review
Today it is generally accepted that there are several endocytic mechanisms, both the clathrin-dependent one and mechanisms which operate without clathrin and with different requirements when it comes to dynamin, small GTP-binding proteins of the Rho family and specific lipids. It should be noted that clathrin-independent endocytosis can occur even when the cholesterol level in the membrane has been reduced to so low levels that caveolae are gone and clathrin-coated membrane areas are flat. Although new investigators in the field take it for granted that there is a multitude of entry mechanisms, it has taken a long time for this to become accepted. However, more work needs to be done, because one can still ask the question: How many endocytic mechanisms does a cell have, what are their function, and how are they regulated? This article describes some of the history of endocytosis research and attempts to give an overview of the complexity of the mechanisms and their regulation.
Topics: ADP-Ribosylation Factors; Actins; Animals; Caveolae; Clathrin; Endocytosis; Epithelial Cells; Humans; Membrane Lipids; Pinocytosis; rho GTP-Binding Proteins
PubMed: 18193449
DOI: 10.1007/s00418-007-0376-5 -
Frontiers in Immunology 2019There are several lines of evidence indicating that the physiopathological bases of bullous pemphigoid (BP), the most common subepidermal autoimmune bullous disease, are... (Review)
Review
There are several lines of evidence indicating that the physiopathological bases of bullous pemphigoid (BP), the most common subepidermal autoimmune bullous disease, are hallmarked by the production of autoantibodies directed against the hemidesmosomal anchoring proteins BP180 and BP230. In contrast to the robustness of the latter assumption, the multifaceted complexity of upstream and downstream mechanisms implied in the pathogenesis of BP remains an area of intense speculation. So far, an imbalance between T regulatory cells and autoreactive T helper (Th) cells has been regarded as the main pathogenic factor triggering the autoimmune response in BP patients. However, the contributory role of signaling pathways fostering the B cell stimulation, such as Toll-like receptor activation, as well as that of ancillary inflammatory mechanisms responsible for blister formation, such as Th17 axis stimulation and the activation of the coagulation cascade, are still a matter of debate. In the same way, the pathomechanisms implied in the loss of dermal-epidermal adhesion secondary to autoantibodies binding are not fully understood. Herein, we review in detail the current concepts and controversies on the complex pathogenesis of BP, shedding light on the most recent theories emerging from the literature.
Topics: Autoantibodies; Autoantigens; Autoimmunity; Blood Coagulation; Comorbidity; Complement Activation; Dystonin; Humans; Leukocytes; Neurodegenerative Diseases; Non-Fibrillar Collagens; Pemphigoid, Bullous; Pinocytosis; Thrombosis; Vitamin D Deficiency; Collagen Type XVII
PubMed: 31312206
DOI: 10.3389/fimmu.2019.01506