Efferocytosisefferocytosis, efferocytosis definition
In cell biology, efferocytosis from efferre, Latin for 'to take to the grave', 'to bury' is the process by which dying/dead cells eg apoptotic or necrotic are removed by phagocytic cells It can be regarded as the 'burying of dead cells'
During efferocytosis, the cell membrane of phagocytic cells engulfs the apoptotic cell, forming a large fluid-filled vesicle containing the dead cell This ingested vesicle is called an efferosome in analogy to the term phagosome This process is similar to macropinocytosis
For apoptosis, the effect of efferocytosis is that dead cells are removed before their membrane integrity is breached and their contents leak into the surrounding tissue This prevents exposure of tissue to toxic enzymes, oxidants and other intracellular components such as proteases and caspases
Efferocytosis can be performed not only by 'professional' phagocytic cells such as macrophages or dendritic cells, but also by many other cell types including epithelial cells and fibroblasts To distinguish them from living cells, apoptotic cells carry specific 'eat me' signals, such as the presence of phosphatidyl serine resulting from phospholipid flip-flop or calreticulin on the outer leaflet of the cell membrane
Efferocytosis triggers specific downstream intracellular signal transduction pathways, for example resulting in anti-inflammatory, anti-protease and growth-promoting effects Conversely, impaired efferocytosis has been linked to autoimmune disease and tissue damage Efferocytosis results in production by the ingesting cell of mediators such as hepatocyte- and vascular endothelial growth factor, which are thought to promote replacement of the dead cells
Defective efferocytosis has been demonstrated in such diseases as cystic fibrosis and bronchiectasis, COPD, asthma and idiopathic pulmonary fibrosis, rheumatoid arthritis, systemic lupus erythematosus, glomerulonephritis and atherosclerosis
Specialized pro-resolving mediators are cell-derived metabolites of certain polyunsaturated fatty acids viz: arachidonic acid which is metabolized to the lipoxins; eicosapentaenoic acid which is metabolized to the Resolvin E's; docosahexaenoic acid which is metablized to the Resolvin D's, Maresins, and Neuroprotectins; and n-3 docosapentaenoic acid which is metabolized to the n-3 docosapentaenoic acid-derived resolvins and n-3 docosapentaenoic acid-derived neuroprotectins See Specialized pro-resolving mediators These mediators possess a broad range of overlapping activities which act to resolve inflammation; one of the important activities which many of these mediators possess is the stimulation of efferocytosis in inflamed tissues Failure to form sufficient amounts of these mediators is proposed to be one cause of chronic and pathological inflammatory responses see Specialized pro-resolving mediators#SPM and inflammation
- ^ deCathelineau AM, Henson PM 2003 "The final step in programmed cell death: phagocytes carry apoptotic cells to the grave" Essays Biochem 39: 105–17 PMID 14585077
- ^ a b c Vandivier RW, Henson PM, Douglas IS June 2006 "Burying the dead: the impact of failed apoptotic cell removal efferocytosis on chronic inflammatory lung disease" Chest 129 6: 1673–82 doi:101378/chest12961673 PMID 16778289
- ^ Gardai SJ, McPhillips KA, Frasch SC, et al October 2005 "Cell-surface calreticulin initiates clearance of viable or apoptotic cells through trans-activation of LRP on the phagocyte" Cell 123 2: 321–34 doi:101016/jcell200508032 PMID 16239148
- ^ Haworth O, Buckley CD 2015 "Pathways involved in the resolution of inflammatory joint disease" Seminars in Immunology 27 3: 194–9 doi:101016/jsmim201504002 PMID 25944272
- ^ Shinohara M, Serhan CN 2016 "Novel Endogenous Proresolving Molecules:Essential Fatty Acid-Derived and Gaseous Mediators in the Resolution of Inflammation" Journal of Atherosclerosis and Thrombosis 23 6: 655–64 doi:105551/jat33928 PMID 27052783
- ^ Basil MC, Levy BD 2016 "Specialized pro-resolving mediators: endogenous regulators of infection and inflammation" Nature Reviews Immunology 16 1: 51–67 doi:101038/nri20154 PMC 5242505 PMID 26688348
|Mechanisms for chemical transport through biological membranes|
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