Редактирование: CD47

Leukocyte surface antigen CD47 precursor (Antigenic surface determinant protein OA3) (Integrin-associated protein) (IAP) (Protein MER6) (CD47 antigen) [MER6]

==Publications==

{{medline-entry
|title=Aging-associated changes in [[CD47]] arrangement and interaction with thrombospondin-1 on red blood cells visualized by super-resolution imaging.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32866348
|abstract=[[CD47]] serves as a ligand for signaling regulatory protein α (SIRPα) and as a receptor for thrombospondin-1 (TSP-1). Although [[CD47]], TSP-1, and SIRPα are thought to be involved in the clearance of aged red blood cells (RBCs), aging-associated changes in the expression and interaction of these molecules on RBCs have been elusive. Using direct stochastic optical reconstruction microscopy (dSTORM)-based imaging and quantitative analysis, we can report that [[CD47]] molecules on young RBCs reside as nanoclusters with little binding to TSP-1, suggesting a minimal role for TSP-1/[[CD47]] signaling in normal RBCs. On aged RBCs, [[CD47]] molecules decreased in number but formed bigger and denser clusters, with increased ability to bind TSP-1. Exposure of aged RBCs to TSP-1 resulted in a further increase in the size of [[CD47]] clusters via a lipid raft-dependent mechanism. Furthermore, [[CD47]] cluster formation was dramatically inhibited on thbs1  mouse RBCs and associated with a significantly prolonged RBC lifespan. These results indicate that the strength of [[CD47]] binding to its ligand TSP-1 is predominantly determined by the distribution pattern and not the amount of [[CD47]] molecules on RBCs, and offer direct evidence for the role of TSP-1 in phagocytosis of aged RBCs. This study provides clear nanoscale pictures of aging-associated changes in [[CD47]] distribution and TSP-1/[[CD47]] interaction on the cell surface, and insights into the molecular basis for how these molecules coordinate to remove aged RBCs.

|keywords=* CD47
* aging
* dSTORM
* red blood cells
* thrombospondin-1
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7576236
}}
{{medline-entry
|title=[[CD47]] Promotes Age-Associated Deterioration in Angiogenesis, Blood Flow and Glucose Homeostasis.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32679764
|abstract=The aged population is currently at its highest level in human history and is expected to increase further in the coming years. In humans, aging is accompanied by impaired angiogenesis, diminished blood flow and altered metabolism, among others. A cellular mechanism that impinges upon these manifestations of aging can be a suitable target for therapeutic intervention. Here we identify cell surface receptor [[CD47]] as a novel age-sensitive driver of vascular and metabolic dysfunction. With the natural aging process, [[CD47]] and its ligand thrombospondin-1 were increased, concurrent with a reduction of self-renewal transcription factors OCT4, [[SOX2]], [[KLF4]] and cMYC (OSKM) in arteries from aged wild-type mice and older human subjects compared to younger controls. These perturbations were prevented in arteries from aged [[CD47]]-null mice. Arterial endothelial cells isolated from aged wild-type mice displayed cellular exhaustion with decreased proliferation, migration and tube formation compared to cells from aged [[CD47]]-null mice. [[CD47]] suppressed ex vivo sprouting, in vivo angiogenesis and skeletal muscle blood flow in aged wild-type mice. Treatment of arteries from older humans with a [[CD47]] blocking antibody mitigated the age-related deterioration in angiogenesis. Finally, aged [[CD47]]-null mice were resistant to age- and diet-associated weight gain, glucose intolerance and insulin desensitization. These results indicate that the [[CD47]]-mediated signaling maladapts during aging to broadly impair endothelial self-renewal, angiogenesis, perfusion and glucose homeostasis. Our findings provide a strong rationale for therapeutically targeting [[CD47]] to minimize these dysfunctions during aging.

|keywords=* CD47
* aging
* angiogenesis
* blood flow
* endothelial cells
* glucose homeostasis
* metabolism
* self-renewal
* thrombospondin-1
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7407670
}}
{{medline-entry
|title=Unique Spatial Immune Profiling in Pancreatic Ductal Adenocarcinoma with Enrichment of Exhausted and Senescent T Cells and Diffused [[CD47]]-SIRPα Expression.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32645996
|abstract=Pancreatic ductal adenocarcinoma (PDAC) is resistant to single-agent immunotherapies. To understand the mechanisms leading to the poor response to this treatment, a better understanding of the PDAC immune landscape is required. The present work aims to study the immune profile in PDAC in relationship to spatial heterogeneity of the tissue microenvironment (TME) in intact tissues. Serial section and multiplex in situ analysis were performed in 42 PDAC samples to assess gene and protein expression at single-cell resolution in the: (a) tumor center (TC), (b) invasive front (IF), (c) normal parenchyma adjacent to the tumor, and (d) tumor positive and negative draining lymph nodes (LNs). We observed: (a) enrichment of T cell subpopulations with exhausted and senescent phenotype in the TC, IF and tumor positive LNs; (b) a dominant type 2 immune response in the TME, which is more pronounced in the TC; (c) an emerging role of [[CD47]]-SIRPα axis; and (d) a similar immune cell topography independently of the neoadjuvant chemotherapy. This study reveals the existence of dysfunctional T lymphocytes with specific spatial distribution, thus opening a new dimension both conceptually and mechanistically in tumor-stroma interaction in PDAC with potential impact on the efficacy of immune-regulatory therapeutic modalities.

|keywords=* CD47
* T cell exhaustion
* T cell senescence
* draining lymph nodes
* macrophage checkpoint
* neoadjuvant chemotherapy
* pancreatic ductal adenocarcinoma
* signal regulatory protein alpha (SIRPα)
* spatial heterogeneity
* tumor microenvironment
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7408661
}}
{{medline-entry
|title=Diabetes Impairs Angiogenesis and Induces Endothelial Cell Senescence by Up-Regulating Thrombospondin-[[CD47]]-Dependent Signaling.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30720765
|abstract=Endothelial dysfunction, impaired angiogenesis and cellular senescence in type 2 diabetes constitute dominant risk factors for chronic non-healing wounds and other cardiovascular disorders. Studying these phenomena in the context of diabetes and the TSP1-CD-47 signaling dictated the use of the in vitro wound endothelial cultured system and an in vivo PVA sponge model of angiogenesis. Herein we report that diabetes impaired the in vivo sponge angiogenic capacity by decreasing cell proliferation, fibrovascular invasion and capillary density. In contrast, a heightened state of oxidative stress and elevated expression of TSP1 and [[CD47]] both at the mRNA and protein levels were evident in this diabetic sponge model of wound healing. An in vitro culturing system involving wound endothelial cells confirmed the increase in ROS generation and the up-regulation of TSP1-[[CD47]] signaling as a function of diabetes. We also provided evidence that diabetic wound endothelial cells (W-ECs) exhibited a characteristic feature that is consistent with cellular senescence. Indeed, enhanced SA-β-gal activity, cell cycle arrest, increased cell cycle inhibitors (CKIs) p53, p21 and p16 and decreased cell cycle promoters including Cyclin D1 and CDK4/6 were all demonstrated in these cells. The functional consequence of this cascade of events was illustrated by a marked reduction in diabetic endothelial cell proliferation, migration and tube formation. A genetic-based strategy in diabetic W-ECs using [[CD47]] siRNA significantly ameliorated in these cells the excessiveness in oxidative stress, attenuation in angiogenic potential and more importantly the inhibition in cell cycle progression and its companion cellular senescence. To this end, the current data provide evidence linking the overexpression of TSP1-[[CD47]] signaling in diabetes to a number of parameters associated with endothelial dysfunction including impaired angiogenesis, cellular senescence and a heightened state of oxidative stress. Moreover, it may also point to TSP1-[[CD47]] as a potential therapeutic target in the treatment of the aforementioned pathologies.
|mesh-terms=* Animals
* CD47 Antigen
* Cell Proliferation
* Cellular Senescence
* Diabetes Mellitus, Type 2
* Disease Models, Animal
* Endothelial Cells
* Female
* Gene Expression Regulation
* Neovascularization, Physiologic
* Oxidative Stress
* Rats
* Signal Transduction
* Thrombospondins
* Wound Healing
|keywords=* cellular senescence TSP1-CD47
* diabetes
* endothelial dysfunction
* impaired angiogenesis
* oxidative stress.
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6386981
}}
{{medline-entry
|title=Loss of complement regulatory proteins on uninfected erythrocytes in vivax and falciparum malaria anemia.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30429373
|abstract=Anemia is a major complication of malaria, driven largely by loss of uninfected RBCs during infection. RBC clearance through loss of complement regulatory proteins ([[CRP]]s) is a significant contributor to anemia in Plasmodium falciparum infection, but its role in Plasmodium vivax infection is unknown. [[CRP]] loss increases RBC susceptibility to macrophage clearance, a process that is also regulated by [[CD47]]. We compared [[CRP]]s and [[CD47]] expression on infected and uninfected RBCs in adult patients with vivax and falciparum malaria and different anemia severities from Papua, Indonesia. Complement activation and parasite-specific complement-fixing antibodies were measured by ELISA. Levels of [[CR1]] and [[CD55]] were reduced in severe anemia in both falciparum and vivax malaria. Loss of [[CRP]]s and [[CD47]] was restricted to uninfected RBCs, with infected RBCs having higher expression. There was no association among complement-fixing antibodies, complement activation, and [[CRP]] loss. Our findings demonstrate that [[CRP]] loss is a pan-species, age-independent mechanism of malarial anemia. Higher levels of [[CRP]] and [[CD47]] expression on infected RBCs suggest that parasites are protected from complement-mediated destruction and macrophage clearance. Lack of associations between protective antibodies and [[CRP]] loss highlight that complement pathogenic and protective pathways are distinct mechanisms during infection.
|mesh-terms=* Adolescent
* Adult
* Aging
* Anemia
* CD47 Antigen
* Complement Activation
* Complement System Proteins
* Erythrocytes
* Female
* Humans
* Malaria, Falciparum
* Malaria, Vivax
* Male
* Plasmodium falciparum
* Plasmodium vivax
* Young Adult
|keywords=* Complement
* Immunology
* Infectious disease
* Malaria
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6303009
}}
{{medline-entry
|title=The matricellular protein TSP1 promotes human and mouse endothelial cell senescence through [[CD47]] and Nox1.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/29042481
|abstract=Senescent cells withdraw from the cell cycle and do not proliferate. The prevalence of senescent compared to normally functioning parenchymal cells increases with age, impairing tissue and organ homeostasis. A contentious principle governing this process has been the redox theory of aging. We linked matricellular protein thrombospondin 1 (TSP1) and its receptor [[CD47]] to the activation of NADPH oxidase 1 (Nox1), but not of the other closely related Nox isoforms, and associated oxidative stress, and to senescence in human cells and aged tissue. In human endothelial cells, TSP1 promoted senescence and attenuated cell cycle progression and proliferation. At the molecular level, TSP1 increased Nox1-dependent generation of reactive oxygen species (ROS), leading to the increased abundance of the transcription factor p53. p53 mediated a DNA damage response that led to senescence through Rb and p21 , both of which inhibit cell cycle progression. Nox1 inhibition blocked the ability of TSP1 to increase p53 nuclear localization and p21  abundance and its ability to promote senescence. Mice lacking TSP1 showed decreases in ROS production, p21  expression, p53 activity, and aging-induced senescence. Conversely, lung tissue from aging humans displayed increases in the abundance of vascular TSP1, Nox1, p53, and p21  Finally, genetic ablation or pharmacological blockade of Nox1 in human endothelial cells attenuated TSP1-mediated ROS generation, restored cell cycle progression, and protected against senescence. Together, our results provide insights into the functional interplay between TSP1 and Nox1 in the regulation of endothelial senescence and suggest potential targets for controlling the aging process at the molecular level.
|mesh-terms=* Adult
* Aged
* Aging
* Animals
* CD47 Antigen
* Cell Line
* Cellular Senescence
* Cyclin-Dependent Kinase Inhibitor p21
* Endothelial Cells
* Female
* Gene Expression Regulation
* Humans
* Lung
* Male
* Mice, Inbred C57BL
* Mice, Knockout
* Middle Aged
* NADPH Oxidase 1
* RNA Interference
* Reactive Oxygen Species
* Signal Transduction
* Thrombospondin 1
* Tumor Suppressor Protein p53

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5679204
}}
{{medline-entry
|title=Thrombospondin-1, Free Radicals, and the Coronary Microcirculation: The Aging Conundrum.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/28762749
|abstract=Successful matching of cardiac metabolism to perfusion is accomplished primarily through vasodilation of the coronary resistance arterioles, but the mechanism that achieves this effect changes significantly as aging progresses and involves the contribution of reactive oxygen species (ROS). Recent Advances: A matricellular protein, thrombospondin-1 (Thbs-1), has been shown to be a prolific contributor to the production and modulation of ROS in large conductance vessels and in the peripheral circulation. Recently, the presence of physiologically relevant circulating Thbs-1 levels was proven to also disrupt vasodilation to nitric oxide (NO) in coronary arterioles from aged animals, negatively impacting coronary blood flow reserve. This review seeks to reconcile how ROS can be successfully utilized as a substrate to mediate vasoreactivity in the coronary microcirculation as "normal" aging progresses, but will also examine how Thbs-1-induced ROS production leads to dysfunctional perfusion and eventual ischemia and why this is more of a concern in advancing age. Current therapies that may effectively disrupt Thbs-1 and its receptor [[CD47]] in the vascular wall and areas for future exploration will be discussed. Antioxid. Redox Signal. 27, 785-801.
|mesh-terms=* Aging
* Animals
* Coronary Circulation
* Free Radicals
* Hemodynamics
* Humans
* Microcirculation
* Nitric Oxide
* Reactive Oxygen Species
* Thrombospondin 1
|keywords=* CD47
* age
* blood flow
* cardiac
* microvessel
* reactive oxygen species
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5647494
}}
{{medline-entry
|title=Physiological levels of thrombospondin-1 decrease NO-dependent vasodilation in coronary microvessels from aged rats.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/27199114
|abstract=Aging and cardiovascular disease are associated with the loss of nitric oxide (NO) signaling and a decline in the ability to increase coronary blood flow reserve (CFR). Thrombospondin-1 (Thbs-1), through binding of [[CD47]], has been shown to limit NO-dependent vasodilation in peripheral vascular beds via formation of superoxide (O2 (-)). The present study tests the hypothesis that, similar to the peripheral vasculature, blocking [[CD47]] will improve NO-mediated vasoreactivity in coronary arterioles from aged individuals, resulting in improved CFR. Isolated coronary arterioles from young (4 mo) or old (24 mo) female Fischer 344 rats were challenged with the NO donor, DEA-[[NONO]]-ate (1 × 10(-7) to 1 × 10(-4) M), and vessel relaxation and O2 (-) production was measured before and after Thbs-1, α[[CD47]], and/or Tempol and catalase exposure. In vivo CFR was determined in anesthetized rats (1-3% isoflurane-balance O2) via injected microspheres following control IgG or α[[CD47]] treatment (45 min). Isolated coronary arterioles from young and old rats relax similarly to exogenous NO, but addition of 2.2 nM Thbs-1 inhibited NO-mediated vasodilation by 24% in old rats, whereas young vessels were unaffected. Thbs-1 increased O2 (-) production in coronary arterioles from rats of both ages, but this was exaggerated in old rats. The addition of [[CD47]] blocking antibody completely restored NO-dependent vasodilation in isolated arterioles from aged rats and attenuated O2 (-) production. Furthermore, α[[CD47]] treatment increased CFR from 9.6 ± 9.3 (IgG) to 84.0 ± 23% in the left ventricle in intact, aged animals. These findings suggest that the influence of Thbs-1 and [[CD47]] on coronary perfusion increases with aging and may be therapeutically targeted to reverse coronary microvascular dysfunction.
|mesh-terms=* Aging
* Animals
* Arterioles
* Coronary Vessels
* Endothelium, Vascular
* Female
* Hydrazines
* Nitric Oxide Donors
* Rats
* Rats, Inbred F344
* Thrombospondin 1
* Vasodilation
|keywords=* CD47
* aging
* coronary blood flow
* nitric oxide
* thrombospondin-1
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6345213
}}
{{medline-entry
|title=Brain innate immunity in the regulation of neuroinflammation: therapeutic strategies by modulating [[CD200]]-[[CD200]]R interaction involve the cannabinoid system.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/24588829
|abstract=The central nervous system (CNS) innate immune response includes an arsenal of molecules and receptors expressed by professional phagocytes, glial cells and neurons that is involved in host defence and clearance of toxic and dangerous cell debris. However, any uncontrolled innate immune responses within the CNS are widely recognized as playing a major role in the development of autoimmune disorders and neurodegeneration, with multiple sclerosis (MS) Alzheimer's disease (AD) being primary examples. Hence, it is important to identify the key regulatory mechanisms involved in the control of CNS innate immunity and which could be harnessed to explore novel therapeutic avenues. Neuroimmune regulatory proteins (NIReg) such as CD95L, [[CD200]], [[CD47]], sialic acid, complement regulatory proteins (CD55, [[CD46]], fH, C3a), [[HMGB1]], may control the adverse immune responses in health and diseases. In the absence of these regulators, when neurons die by apoptosis, become infected or damaged, microglia and infiltrating immune cells are free to cause injury as well as an adverse inflammatory response in acute and chronic settings. We will herein provide new emphasis on the role of the pair [[CD200]]-[[CD200]]R in MS and its experimental models: experimental autoimmune encephalomyelitis (EAE) and Theiler's virus induced demyelinating disease (TMEV-IDD). The interest of the cannabinoid system as inhibitor of inflammation prompt us to introduce our findings about the role of endocannabinoids (eCBs) in promoting [[CD200]]-[[CD200]] receptor ([[CD200]]R) interaction and the benefits caused in TMEV-IDD. Finally, we also review the current data on [[CD200]]-[[CD200]]R interaction in AD, as well as, in the aging brain.
|mesh-terms=* Aging
* Alzheimer Disease
* Antigens, CD
* Antigens, Surface
* Brain
* Encephalitis
* Endocannabinoids
* Humans
* Immunity, Innate
* Multiple Sclerosis
* Orexin Receptors
* Receptors, Cell Surface

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4157566
}}
{{medline-entry
|title=Mechanisms tagging senescent red blood cells for clearance in healthy humans.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/24399969
|abstract=This review focuses on the analysis and evaluation of the diverse senescence markers suggested to prime red blood cells (RBC) for clearance in humans. These tags develop in the course of biochemical and structural alterations accompanying RBC aging, as the decrease of activities of multiple enzymes, the gradual accumulation of oxidative damage, the loss of membrane in form of microvesicles, the redistribution of ions and alterations in cell volume, density, and deformability. The actual tags represent the penultimate galactosyl residues, revealed by desialylation of glycophorins, or the aggregates of the anion exchanger (band 3 protein) to which anti-galactose antibodies bind in the first and anti-band 3 naturally occurring antibodies (NAbs) in the second case. While anti-band 3 NAbs bind to the carbohydrate-free portion of band 3 aggregates in healthy humans, induced anti-lactoferrin antibodies bind to the carbohydrate-containing portion of band 3 and along with anti-band 3 NAbs may accelerated clearance of senescent RBC in patients with anti-neutrophil cytoplasmic antibodies (ANCA). Exoplasmically accessible phosphatidylserine (PS) and the alterations in the interplay between [[CD47]] on RBC and its receptor on macrophages, signal regulatory protein alpha (SIRPalpha protein), were also reported to induce erythrocyte clearance. We discuss the relevance of each mechanism and analyze the strength of the data. 

|keywords=* hemoglobin
* human red blood cells
* naturally occurring antibodies
* oxidative stress
* senescence
* vesicles
* volume
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3872327
}}
{{medline-entry
|title=A Double in vivo Biotinylation Technique for Objective Assessment of Aging and Clearance of Mouse Erythrocytes in Blood Circulation.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/23801925
|abstract=We have recently developed a new technique to objectively identify erythrocyte cohorts of defined age in mouse blood. The technique (termed double in vivo biotinylation, DIB) involves an initial biotinylation of all erythrocytes in circulation, followed after a few days by a second biotinylation, at a lower density, that labels the biotin-negative erythrocytes that have entered since the first biotinylation. The proportions of biotin(high), biotin(low), and biotin(negative) erythrocytes are enumerated by flow cytometry. The DIB technique allows us to track age-related changes on erythrocyte cohorts (Protocol A), and to simultaneously identify very young and older erythrocyte populations in the blood (Protocol B). Using this technique, we have reexamined: i) the relationship between age and buoyant density of erythrocytes, ii) erythrocyte destruction through a random removal mechanism, and iii) the expression of phosphatidylserine on aging erythrocytes. We have also used the DIB technique to study age-related changes in the expression of various markers like [[CD47]] and CD147 and green autofluorescence in aging erythrocyte populations.

|keywords=* Double in vivo biotinylation
* Erythrocyte aging
* Erythrocyte removal
* Mouse blood circulation
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3678280
}}