Efferocytosis and Its Role in Inflammatory Disorders

Ge, Yun; Huang, Man; Yao, Yong‐Ming

doi:10.3389/fcell.2022.839248

Cited by 56 publications

(47 citation statements)

References 158 publications

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“…In eryptotic erythrocytes, PS molecules are translocated to the outer leaflet of phospholipid bilayer and this hallmark of eryptosis facilitates uptake of eryptotic RBCs by phagocytic cells via the process called efferocytosis. Selective recognition of PS 'eat-me' signals and clearance of eryptotic cells via efferocytosis diminishes the release of DAMPs and modifies the macrophage phenotype downregulating pro-inflammatory cytokines [72]. Thus, it can be postulated that eryptosis should be triggered by lower concentrations of xenobiotics compared with hemolysis.…”

Section: Discussionmentioning

confidence: 99%

Hemocompatibility of dextran-graft-polyacrylamide/zinc oxide nanosystems: hemolysis or eryptosis?

Onishchenko,

Prokopiuk,

Chumachenko

et al. 2023

Nanotechnology

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Aim. In this study, blood compatibility of ZnO nanoparticles-nanocomplex (D-PAA/ZnONPs(SO42-)) synthesized in situ into dextran-graft-polyacrylamide (D-PAA) using zinc oxide nanoparticles produced from zinc sulphate (D-PAA/ZnONPs(SO42-)) as a precursor was tested using hemolysis, osmotic fragility and eryptosis assays.Materials and methods. Dose-dependent ability to induce eryptosis was assessed following 24 h incubation at concentrations of 0-800 mg / L analyzing hallmarks of eryptosis (cell shrinkage and phosphatidylserine externalization), as well as reactive oxygen species (ROS) generation. Hemolysis was detected spectrophotometrically based on hemoglobin release following exposure to the D-PAA/ZnONPs(SO42-) nanocomplex. Osmotic fragility test (OFT) involved detection of hemolysis of red blood cells exposed to 0.2% saline solution following incubation with the D-PAA/ZnONPs(SO42-) nanocomplex. Additional incubation of the nanocomplex in the presence or absence of either ascorbic acid or EGTA was used to reveal the implication of oxidative stress- or Ca2+-mediated mechanisms in D-PAA/ZnONPs(SO42-) nanocomplex-induced erythrotoxicity.Results. Hemocompatibility assessment of the D-PAA/ZnONPs(SO42-) nanocomplex revealed that it induced hemolysis and reduced resistance of erythrocytes to osmotic stress at concentrations of above 400 and 200 mg / L, respectively. Oxidative stress- or Ca2+-mediated mechanisms were not involved in D-PAA/ZnONPs(SO42-) nanocomplex-induced hemolysis. Strikingly, the D-PAA/ZnONPs(SO42-) nanocomplex did not promote cell membrane scrambling, cell shrinkage and oxidative stress in red blood cells following the direct exposure for 24 h. Thus, the D-PAA/ZnONPs(SO42-) nanocomplex did not induce eryptosis in vitro. Eryptosis is generally considered to occur earlier than hemolysis in response to stress in order to prevent hemolytic cell death. Counterintuitively, our data suggest that hemolysis can be triggered by nanomaterials prior to eryptosis indicating that eryptosis and hemolysis assays should be used in combination for testing blood compatibility of nanomaterials. Conclusions. The D-PAA/ZnONPs(SO42-) nanocomplex has a good hemocompatibility profile at low concentrations. Hemocompatibility testing in nanotoxicology should include both eryptosis and hemolysis assays. 

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Section: Discussionmentioning

confidence: 99%

Hemocompatibility of dextran-graft-polyacrylamide/zinc oxide nanosystems: hemolysis or eryptosis?

Onishchenko,

Prokopiuk,

Chumachenko

et al. 2023

Nanotechnology

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“…Efferocytosis is compensated by four steps: (1) phagocyte recruitment controlled by find-me signals, (2) dead cell recognition controlled by eat-me signals, (3) dead cell absorption and (4) dying cell degradation [ 23 , 88 ]. Healthy cells send tolerate I signals, also known as ‘keep-me’ or ‘do not eat-me’ signals, to prevent efferocytosis [ 15 ]. Some receptors, such as complement and antibody Fc receptors, communicate with the cytoskeleton and initiate direct phagocytic activity in response to eat-me signals, whereas others, such as the TIM-4 receptor, only anchor the target cell [ 89 , 90 ].…”

Section: Efferocytosis Of Necroptosis and Pyroptosismentioning

confidence: 99%

“…Apoptotic cells emit find-me signals in order to distinguish themselves from healthy cells and to attract phagocytes to areas of death [ 15 ]. These signals primarily function as DAMPs, promoting the production of a variety of cytokines and chemokines that activate phagocytes [ 3 , 4 ].…”

Section: Efferocytosis Of Necroptosis and Pyroptosismentioning

confidence: 99%

“…Lesional efferocytosis and larger necrotic cores were associated with low-density lipoprotein receptor deficiencies in chronic diseases when compared to healthy animals. Inadequate efferocytosis is a common diabetic side effect that can prevent tissue repair and lead to chronic inflammation as a result of a build-up of apoptotic cells at the wound site [ 15 ]. The molecular pathway of efferocytosis in necroptosis and pyroptosis is less well understood than the apoptosis mechanism.…”

Section: Introductionmentioning

confidence: 99%

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Update of cellular responses to the efferocytosis of necroptosis and pyroptosis

et al. 2023

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Cell death is a basic physiological process that occurs in all living organisms. A few key players in these mechanisms, as well as various forms of cell death programming, have been identified. Apoptotic cell phagocytosis, also known as apoptotic cell clearance, is a well-established process regulated by a number of molecular components, including ‘find-me’, ‘eat-me’ and engulfment signals. Efferocytosis, or the rapid phagocytic clearance of cell death, is a critical mechanism for tissue homeostasis. Despite having similar mechanism to phagocytic clearance of infections, efferocytosis differs from phagocytosis in that it induces a tissue-healing response and is immunologically inert. However, as field of cell death has rapid expanded, much attention has recently been drawn to the efferocytosis of additional necrotic-like cell types, such as necroptosis and pyroptosis. Unlike apoptosis, this method of cell suicide allows the release of immunogenic cellular material and causes inflammation. Regardless of the cause of cell death, the clearance of dead cells is a necessary function to avoid uncontrolled synthesis of pro-inflammatory molecules and inflammatory disorder. We compare and contrast apoptosis, necroptosis and pyroptosis, as well as the various molecular mechanisms of efferocytosis in each type of cell death, and investigate how these may have functional effects on different intracellular organelles and signalling networks. Understanding how efferocytic cells react to necroptotic and pyroptotic cell uptake can help us understand how to modulate these cell death processes for therapeutic purposes.

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“…They phagocytose apoptotic neutrophils by efferocytosis, help in repair of tissue following injury. They are also mediators in fibrosis, tumor growth and immunosuppression ( Ge et al, 2022 ). MΦs exhibit their functions by promoting release of proinflammatory mediators, presenting antigens to naive T lymphocytes thereby stimulating adaptive immune response in the tissue ( Di Benedetto et al, 2019 ).…”

Section: Spms In Regulation Of Inflammatory Macrophages In Covid-19mentioning

confidence: 99%

Specialized pro-resolving lipid mediators regulate inflammatory macrophages: A paradigm shift from antibiotics to immunotherapy for mitigating COVID-19 pandemic

Kumar

Yasmeen²,

Chaudhary³

et al. 2023

Front. Mol. Biosci.

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The most severe clinical manifestations of the horrifying COVID-19 disease, that claimed millions of lives during the pandemic time, were Acute respiratory distress syndrome (ARDS), Coagulopathies, septic shock leading eventually to death. ARDS was a consequence of Cytokine storm. The viral SARS-COV2infection lead to avalanche of cytokines and eicosanoids causing “cytokine storm” and “eicosanoid storm.” Cytokine storm is one of the macrophage-derived inflammatory responses triggered by binding of virus particles to ACE2 receptors of alveolar macrophages, arise mainly due to over production of various pro-inflammatory mediators like cytokines, e.g., interleukin (IL)-1, IL-2, and tumor necrosis factor (TNF)- α, causing pulmonary edema, acute respiratory distress, and multi-organ failure. Cytokine storm was regarded as the predictor of severity of the disease and was deemed one of the causes of the high mortality rates due to the COVID-19. The basis of cytokine storm is imbalanced switching between an inflammation increasing - pro-inflammatory (M1) and an inflammation regulating-anti-inflammatory (M2) forms of alveolar macrophages which further deteriorates if opportunistic secondary bacterial infections prevail in the lungs. Lack of sufficient knowledge regarding the virus and its influence on co-morbidities, clinical treatment of the diseases included exorbitant use of antibiotics to mitigate secondary bacterial infections, which led to the unwarranted development of multidrug resistance (MDR) among the population across the globe. Antimicrobial resistance (AMR) needs to be addressed from various perspectives as it may deprive future generations of the basic health immunity. Specialized pro-resolving mediators (SPMs) are generated from the stereoselective enzymatic conversions of essential fatty acids that serve as immune resolvents in controlling acute inflammatory responses. SPMs facilitate the clearance of injured tissue and cell debris, the removal of pathogens, and augment the concentration of anti-inflammatory lipid mediators. The SPMs, e.g., lipoxins, protectins, and resolvins have been implicated in exerting inhibitory influence on with cytokine storm. Experimental evidence suggests that SPMS lower antibiotic requirement. Therefore, in this review potential roles of SPMs in enhancing macrophage polarization, triggering immunological functions, hastening inflammation resolution, subsiding cytokine storm and decreasing antibiotic requirement that can reduce AMR load are discussed.

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Efferocytosis and Its Role in Inflammatory Disorders

Cited by 56 publications

References 158 publications

Hemocompatibility of dextran-graft-polyacrylamide/zinc oxide nanosystems: hemolysis or eryptosis?

Hemocompatibility of dextran-graft-polyacrylamide/zinc oxide nanosystems: hemolysis or eryptosis?

Update of cellular responses to the efferocytosis of necroptosis and pyroptosis

Specialized pro-resolving lipid mediators regulate inflammatory macrophages: A paradigm shift from antibiotics to immunotherapy for mitigating COVID-19 pandemic

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