Efferocytosis refers to the process of phagocytes engulfing and clearing the cells after programmed cell death. In recent years, an increasing number of studies have shown that the mechanisms of efferocytosis are closely related to drug-induced liver injury, hepatic ischemia-reperfusion injury, viral hepatitis, cholestatic liver diseases, metabolic-associated fatty liver disease, alcoholic liver disease, and other liver disorders. This review summarized the research progress on the role of efferocytosis in liver diseases, with the hope of providing new targets for the prevention and treatment of liver diseases.
Humans ; Liver Diseases/metabolism* ; Animals ; Phagocytosis/physiology* ; Phagocytes ; Efferocytosis

Efferocytosis refers to the process that phagocytes recognize and remove the apoptotic cells, which is essential for maintaining tissue homeostasis both in physiological and pathological conditions. Numerous studies have demonstrated that efferocytosis can prevent secondary necrosis and proinflammatory factor release, leading to the resolution of inflammation and tissue immunological tolerance in numerous diseases such as stroke. Stroke is a leading cause of death and morbidity for adults worldwide. Persistent inflammation triggered by the dead cells or cell debris is a major contributor to post-stroke brain damage. Effective efferocytosis might be an efficient strategy to minimize inflammation and restore brain homeostasis for neuronal regeneration and function recovery. In this review, we will discuss the phagocytes in the brain, the molecular mechanisms underlying efferocytosis, the role of efferocytosis in inflammation resolution, and the potential therapeutic applications targeting efferocytosis in stroke.
Humans ; Stroke ; Phagocytosis/physiology* ; Inflammation ; Apoptosis/physiology* ; Animals ; Phagocytes/physiology* ; Brain/metabolism* ; Efferocytosis

Autophagy is a highly conserved intracellular degradation and energy-recycling mechanism that contributes to the maintenance of cellular homeostasis. Extensive researches over the past decades have defined the role of autophagy innate immune cells. In this review, we describe the current state of knowledge regarding the role of autophagy in neutrophil biology and a picture of molecular mechanism underlying autophagy in neutrophils. Neutrophils are professional phagocytes that comprise the first line of defense against pathogen. Autophagy machineries are highly conserved in neutrophils. Autophagy is not only involved in generalized function of neutrophils such as differentiation in bone marrow but also plays crucial role effector functions of neutrophils such as granule formation, degranulation, neutrophil extracellular traps release, cytokine production, bactericidal activity and controlling inflammation. This review outlines the current understanding of autophagy in neutrophils and provides insight towards identification of novel therapeutics targeting autophagy in neutrophils.
Autophagy ; Biology ; Bone Marrow ; Extracellular Traps ; Homeostasis ; Inflammation ; Neutrophils ; Phagocytes

BACKGROUND: Retinal degeneration causes blindness, and cell replacement is a potential therapy. The purpose of this study is to formation of pigmented neurospheres in a simple medium, low-cost, high-performance manner over a short period of time while expressing markers of RPE cells and the activation of specific genes of the pigment cells. Also, these neurospheres have the ability to produce a monolayer of retinal pigment epithelium-like cells (RPELC) with the ability of photoreceptor outer segment phagocytosis. METHODS: BMSC were isolated from pigmented hooded male rats and were immunoreactive to BMSC markers, then converted into neurospheres, differentiated into pigmented spheres (PS), and characterized using Retinal pigment epithelium-specific 65 kDa protein (RPE65), Retinaldehyde-binding protein 1 (CRALBP) and orthodenticle homeobox 2 (OTX2) markers by immunocytochemistry, RT-PCR and RT-qPCR. The PS were harvested into RPELC. The functionality of RPELC was evaluated by phagocytosis of fluorescein-labeled photoreceptor outer segment. RESULTS: The BMSC immunophenotype was confirmed by immunostained for fibronectin, CD90, CD166 and CD44. These cells differentiated into osteogenic and lipogenic cells. The generated neurospheres were immunoreactive to nestin and stemness genes. The PS after 7–14 days were positive for RPE65 (92.76–100%), CRALBP (95.21–100%) and OTX2 (94.88–100%), and after 30 days RT-PCR, qPCR revealed increasing in gene expression. The PS formed a single layer of RPELC after cultivation and phagocyte photoreceptor outer segments. CONCLUSION: Bone marrow stromal stem cells can differentiate into functional retinal pigmented epithelium cells in a simple, low-cost, high-performancemanner over a short period of time. These cells due to expressing theRPELCgenes andmarkers can be used in cell replacement therapy for degenerative diseases including age-relatedmacular degeneration as well as retinitis pigmentosa.
Animals ; Blindness ; Bone Marrow ; Epithelium ; Fibronectins ; Gene Expression ; Genes, Homeobox ; Humans ; Immunohistochemistry ; Male ; Nestin ; Phagocytes ; Phagocytosis ; Rats ; Retinal Degeneration ; Retinal Pigment Epithelium ; Retinaldehyde ; Retinitis Pigmentosa ; Stem Cells

Phagocytosis is a fundamental process in which phagocytes capture and ingest foreign particles including pathogenic bacteria. Several oral pathogens have anti-phagocytic strategies, which allow them to escape from and survive in phagocytes. Impaired bacteria phagocytosis increases inflammation and contributes to inflammatory diseases. The purpose of this study is to investigate the influences of various agents on oral pathogenic phagocytosis. To determine phagocytosis, Streptococcus mutans, Fusobacterium nucleatum, Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis were stained with 5-(and-6)-carboxyfluorescein diacetate succinimidyl ester (CFSE), and was measured using flowcytometery and confocal microscopy. The influencing factors on phagocytosis were evaluated through the pretreatment of ROS inhibitor (N-acetyl-L-cysteine (NAC)), lysozyme, potassium chloride (KCI) and adenosine triphosphate (ATP) in THP-1 cells. Expression of pro-inflammatory cytokines was determined by enzyme-linked immunosorbent assay (ELISA). The phagocytosis of various bacteria increased in a MOI-dependent manner. Among the tested bacteria, phagocytosis of P. gingivalis showed the highest fluorescent intensity at same infection time. Among the tested inhibitors, the NAC treatment significantly inhibited phagocytosis in all tested bacteria. In addition, NAC treatment indicated a similar pattern under the confocal microscopy. Moreover, NAC treatment significantly increased the bacteria-induced secretion of IL-1β among the tested inhibitors. Taken together, we conclude that the phagocytosis occurs differently depending on each bacterium. Down-regulation by ROS production inhibited phagocytosis and lead increased of oral pathogens-associated inflammation.
Adenosine Triphosphate ; Aggregatibacter actinomycetemcomitans ; Bacteria ; Cytokines ; Down-Regulation ; Enzyme-Linked Immunosorbent Assay ; Fusobacterium nucleatum ; Inflammation ; Macrophages ; Microscopy, Confocal ; Monocytes ; Muramidase ; Phagocytes ; Phagocytosis ; Porphyromonas gingivalis ; Potassium Chloride ; Streptococcus mutans ; United Nations

Brucellosis is one of the common zoonoses caused by Brucella abortus (B. abortus). However, little has been reported on factors affecting invasion of B. abortus into host cells. To investigate cell-type dependent invasion of B. abortus, phagocytic RAW 264.7 and THP-1 cells and non-phagocytic HeLa cells were infected with wild-type and mutant B. abortus, and their invasion efficiencies were compared. The invasion efficiencies of the strains were cell-type dependent. Wild-type B. abortus invasion efficiency was greater in phagocytic cells than in epithelial cells. The results also indicated that there are different factors involved in the invasion of B. abortus into phagocytic cells.
Brucella abortus ; Brucella ; Brucellosis ; Epithelial Cells ; HeLa Cells ; Humans ; Phagocytes ; Zoonoses

Extracellular vesicles (EVs) are membrane-derived vesicles that mediate intercellular communications. As professional phagocytes, neutrophils also produce EVs in response to various inflammatory stimuli during inflammatory processes. Neutrophil-derived EVs can be categorized into 2 subtypes according to the mechanism of generation. Neutrophil-derived trails (NDTRs) are generated from migrating neutrophils. The uropods of neutrophils are elongated by adhesion to endothelial cells, and small parts of the uropods are detached, leaving submicrometer-sized NDTRs. Neutrophil-derived microvesicles (NDMVs) are generated from neutrophils which arrived at the inflammatory foci. Membrane blebbing occurs in response to various stimuli at the inflammatory foci, and small parts of the blebs are detached from the neutrophils, leaving NDMVs. These 2 subtypes of neutrophil-derived EVs share common features such as membrane components, receptors, and ligands. However, there are substantial differences between these 2 neutrophil-derived EVs. NDTRs exert pro-inflammatory functions by guiding subsequent immune cells through the inflammatory foci. On the other hand, NDMVs exert anti-inflammatory functions by limiting the excessive immune responses of nearby cells. This review outlines the current understanding of the different subtypes of neutrophil-derived EVs and provides insights into the clinical relevance of neutrophil-derived EVs.
Blister ; Endothelial Cells ; Extracellular Vesicles* ; Hand ; Ligands ; Membranes ; Neutrophils* ; Phagocytes

Acute kidney injury is a clinical syndrome that can be caused by numerous diseases including acute tubular necrosis (ATN). ATN evolves in several phases, all of which are accompanied by different immune mechanisms as an integral component of the disease process. In the early injury phase, regulated necrosis, damage-associated molecular patterns, danger sensing, and neutrophil-driven sterile inflammation enhance each other and contribute to the crescendo of necroinflammation and tissue injury. In the late injury phase, renal dysfunction becomes clinically apparent, and M1 macrophage-driven sterile inflammation contributes to ongoing necroinflammation and renal dysfunction. In the recovery phase, M2-macrophages and anti-inflammatory mediators counteract the inflammatory process, and compensatory remnant nephron and cell hypertrophy promote an early functional recovery of renal function, while some tubules are still badly injured and necrotic material is removed by phagocytes. The resolution of inflammation is required to promote the intrinsic regenerative capacity of tubules to replace at least some of the necrotic cells. Several immune mechanisms support this wound-healing-like re-epithelialization process. Similar to wound healing, this response is associated with mesenchymal healing, with a profound immune cell contribution in terms of collagen production and secretion of profibrotic mediators. These and numerous other factors determine whether, in the chronic phase, persistent loss of nephrons and hyperfunction of remnant nephrons will result in stable renal function or progress to decline of renal function such as progressive chronic kidney disease.
Acute Kidney Injury ; Collagen ; Extracellular Traps ; Hypertrophy ; Inflammation ; Necrosis* ; Nephrons ; Phagocytes ; Re-Epithelialization ; Renal Insufficiency, Chronic ; Wound Healing

The clearance of apoptotic cells is an essential process for tissue homeostasis. To this end, cells undergoing apoptosis must display engulfment signals, such as ‘find-me' and ‘eat-me' signals. Engulfment signals are recognized by multiple types of phagocytic machinery in phagocytes, leading to prompt clearance of apoptotic cells. In addition, apoptotic cells and phagocytes release tolerogenic signals to reduce immune responses against apoptotic cell-derived self-antigens. Here we discuss recent advances in our knowledge of engulfment signals, the phagocytic machinery and the signal transduction pathways for apoptotic cell engulfment.
Apoptosis ; Autoantigens ; Homeostasis ; Phagocytes ; Signal Transduction

Group B streptococcus (GBS) infection is a leading cause of sepsis and meningitis among infants, and is associated with high rates of morbidity and mortality in many countries. Protection against GBS typically involves antibody-mediated opsonization by phagocytes and complement components. The present study evaluated serotype-specific functional antibodies to GBS among Korean infants and in intravenous immunoglobulin (IVIG) products. An opsonophagocytic killing assay (OPA) was used to calculate the opsonization indices (OIs) of functional antibodies to serotypes Ia, Ib, and III in 19 IVIG products from 5 international manufacturers and among 98 Korean infants (age: 0–11 months). The GBS Ia, Ib, and III serotypes were selected because they are included in a trivalent GBS vaccine formulation that is being developed. The OI values for the IVIG products were 635–5,706 (serotype Ia), 488–1,421 (serotype Ib), and 962–3,315 (serotype III), and none of the IVIG lots exhibited undetectable OI values (< 4). The geometric mean OI values were similar for all 3 serotypes when we compared the Korean manufacturers. The seropositive rate among infants was significantly lower for serotype Ia (18.4%), compared to serotype Ib and serotype III (both, 38.8%). Infant age of ≥ 3 months was positively correlated with the seropositive rates for each serotype. Therefore, only a limited proportion of infants exhibited protective immunity against serotype Ia, Ib, and III GBS infections. IVIG products that exhibit high antibody titers may be a useful therapeutic or preventive measure for infants. Further studies are needed to evaluate additional serotypes and age groups.
Antibodies* ; Complement System Proteins ; Homicide ; Humans ; Immunoglobulins* ; Immunoglobulins, Intravenous ; Infant* ; Meningitis ; Mortality ; Opsonin Proteins ; Phagocytes ; Sepsis ; Serogroup* ; Streptococcus agalactiae ; Streptococcus*