Like all living organisms, cells ingest foreign bodies, but not always as nutrients. Ingestion is also used to eliminate pathogens such as bacteria or harmful cellular waste. This cell function, known as phagocytosis, is vital, notably to the immune and inflammatory response.
Target enveloping :Once cellular waste are recognized and anchored on membrane;; the assembly of actin filaments starts. The membrane progressively engulfs the waste; what needs a supply of membranes from various internal cellular compartments.When the membrane folds fuse;; the waste is completely ingested by the cell and rendered harmless
Target cells ingested by white blood cells : On picture A;; the white blood cell (big cell) recognised some target cells (little white spheres) to eliminate and anchored them on its membrane. 50 minutes later (picture B);; target cells have been ingested. On pictures C;;D;; and E the white blood cell expresses a mutant type of ARF6 blocked in inactive position. On picture C;; the white blood cell recognised other white blood cells to eliminate and anchored them on its membrane. On picture D;; taken 50 minutes later;; target cells are still anchored on the white blood cells membrane and havent been ingested. On picture E;; the extension of the membrane starts but stops soon. Absorption doesnt occur.
CNRS research scientists at the Institut Curie have recently clarified the function of the protein ARF6 in phagocytosis, a mechanism which is still poorly understood. When ARF6 is lacking, the cells can eliminate neither waste nor pathogenic microorganisms. This breakdown in the "cell cleaning" system may then result in major dysfunction (infection, inflammation) or even compromise the organisms integrity (risk of tumor).
These results are presented in the 23 June 2003 issue of Journal of Cell Biology.
In the case of chronic infection or inflammation, the bodys equilibrium is compromised and there is even the risk of the development of tumors. In particular, a link has been established between Helicobacter pylori infection and the development of gastric cancer, but the mechanisms brought into play in this model of oncogenesis remain poorly understood.
A very recent American publication has provided a clue to the putative link between chronic inflammation and the appearance of cancer: in mice whose phagocytic and immune functions are deficient, chronic infections lead to the growth of spontaneous tumors when the animals are not treated with antibiotics. This is new proof of the importance of phagocytosis, for good functioning of the body.
Envelop then degrade
When "cleaning cells" recognize a target to be eliminated, using their membrane receptors, they anchor it to the membrane. Phagocytosis then starts with the formation of membrane folds, a sort of envelope which progressively engulfs the target until it is internalized within the cell.
The gradual formation of a membrane requires reorganization of actin filaments, the "muscles" of the cell, and remodeling of the membrane. The assembly (polymerization) of actin filaments "pushes" the membrane around the cellular waste by a process analogous to that seen in cell motility (see "Further information on").
To enlarge the surface area of the membrane so as to allow enfolding of cellular waste, a supply of membranes from various internal cellular compartments is indispensable. When the waste is fully enveloped, the membrane folds fuse thereby completely ingesting the waste and rendering it harmless. The waste is then conveyed to vesicles where it is degraded. At this stage antigens are processed and once transported to the surface of cells, will trigger the immune response (acquired immunity).
At the Institut Curie, Philippe Chavriers "Membrane and cytoskeleton dynamics" team is studying the reorganization of the membrane and of the cytoskeleton during phagocytosis. It is focusing in particular on the protein ARF6, which is thought to play a part in phagocytosis and in cell motility, and whose precise function remains to be elucidated.
ARF6 "delivers" membranes
Like many proteins, ARF6 works as a "biological switch" flicking successively between the inactive and active states, during which it fulfils its functions. In this new work, Florence Niedergang of Philippe Chavriers team has demonstrated for the first time that ARF6 is activated during phagocytosis, at the start of the process, suggesting that it plays a part in the early stages of the engulfing of waste.
To study this hypothesis further, researchers at the Institut Curie studied phagocytosis by scanning electron microscopy in cells where ARF6 is blocked in the inactive position. They found that the extension of the membrane around the waste is soon stopped. Furthermore, they noted that the interruption was not due to blockade of actin polymerization but to defective delivery of membranes from the intracellular compartments.
ARF6 therefore plays a crucial role in the delivery of membranes during phagocytosis.
As phagocytosis and cell motility share several features (see below), ARF6 could also be indispensable to cell motility and may be involved in the formation of metastases. The presence of metastases renders cancer treatment more problematical, and so it is important to identify the proteins that participate in this process and which could in time serve as targets for new therapies.
The work of Philippe Chavrier and his team at the Institut Curie therefore provides fundamental information on the mechanisms of phagocytosis, while providing a glimpse of new leads in the understanding of cancerous processes.
Catherine Goupillon | Institut Curie
Superresolution live-cell imaging provides unexpected insights into the dynamic structure of mitochondria
18.02.2020 | Heinrich-Heine-Universität Düsseldorf
Blood and sweat: Wearable medical sensors will get major sensitivity boost
18.02.2020 | Moscow Institute of Physics and Technology
Most natural and artificial surfaces are rough: metals and even glasses that appear smooth to the naked eye can look like jagged mountain ranges under the microscope. There is currently no uniform theory about the origin of this roughness despite it being observed on all scales, from the atomic to the tectonic. Scientists suspect that the rough surface is formed by irreversible plastic deformation that occurs in many processes of mechanical machining of components such as milling.
Prof. Dr. Lars Pastewka from the Simulation group at the Department of Microsystems Engineering at the University of Freiburg and his team have simulated such...
Investigation of the temperature dependence of the skyrmion Hall effect reveals further insights into possible new data storage devices
The joint research project of Johannes Gutenberg University Mainz (JGU) and the Massachusetts Institute of Technology (MIT) that had previously demonstrated...
Researchers at Chalmers University of Technology, Sweden, recently completed a 5-year research project looking at how to make fibre optic communications systems more energy efficient. Among their proposals are smart, error-correcting data chip circuits, which they refined to be 10 times less energy consumptive. The project has yielded several scientific articles, in publications including Nature Communications.
Streaming films and music, scrolling through social media, and using cloud-based storage services are everyday activities now.
After helping develop a new approach for organic synthesis -- carbon-hydrogen functionalization -- scientists at Emory University are now showing how this approach may apply to drug discovery. Nature Catalysis published their most recent work -- a streamlined process for making a three-dimensional scaffold of keen interest to the pharmaceutical industry.
"Our tools open up whole new chemical space for potential drug targets," says Huw Davies, Emory professor of organic chemistry and senior author of the paper.
Superconductivity approaching room temperature may be possible in hydrogen-rich compounds at much lower pressures than previously expected
Reaching room-temperature superconductivity is one of the biggest dreams in physics. Its discovery would bring a technological revolution by providing...
12.02.2020 | Event News
16.01.2020 | Event News
15.01.2020 | Event News
18.02.2020 | Power and Electrical Engineering
18.02.2020 | Information Technology
18.02.2020 | Physics and Astronomy