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

In this study, we observed that lysophosphatidylglycerol (LPG) completely inhibited a formyl peptide receptor like-1 (FPRL1) agonist (MMK-1)-stimulated chemotactic migration in human phagocytes, such as neutrophils and monocytes. LPG also dramatically inhibited IL-1beta production by another FPRL1 agonist serum amyloid A (SAA) in human phagocytes. However, LPG itself induced intracellular calcium increase and superoxide anion production in human phagocytes. Keeping in mind that phagocytes migration and IL-1beta production by FPRL1 are important for the induction of inflammatory response, our data suggest that LPG can be regarded as a useful material for the modulation of inflammatory response induced by FPRL1 activation.
Chemotaxis, Leukocyte/*drug effects ; Humans ; Interleukin-1beta/*biosynthesis ; Lysophospholipids/*pharmacology ; Monocytes/drug effects/immunology/metabolism/physiology ; Neutrophils/drug effects/immunology/metabolism/physiology ; Peptides/metabolism/pharmacology ; *Phagocytes/drug effects/immunology/metabolism/physiology ; Receptors, Formyl Peptide/*metabolism ; Receptors, Lipoxin/*metabolism ; Serum Amyloid A Protein/metabolism/pharmacology

Johne's disease is a condition that refers to chronic granulomatous enteritis in ruminants. It is believed that survival and replication of Mycobacterium (M.) paratuberculosis in mononuclear phagocytes plays an important role in the pathogenesis of Johne's disease. However, it is not clear how M. paratuberculosis survives for long time periods in mononuclear phagocytes, nor is it clear which factors trigger multiplication of these bacilli and result in the development of Johne's disease. Investigating the intracellular fate of M. paratuberculosis is challenging because of its very slow growth (more than two months to form visible colonies on media). Existing animal models also have limitations. Despite those obstacles, there has been progress in understanding the intracellular survival tactics of M. paratuberculosis and the host response against them. In this review, we compare known aspects of the intracellular survival tactics of M. paratuberculosis with those of other mycobacterial species, and consider possible mycobactericidal mechanisms of mononuclear phagocytes.
Animals ; Leukocytes, Mononuclear/*microbiology ; Mycobacterium avium subsp. paratuberculosis/*physiology ; Phagocytes/*microbiology

The immune function of spleen after partial splenectomy (PSM) of rabbits was stuided using microwave tissue coagulation (MTC). Streptococcus pneumoniae suspension was injected into the ear veins of rabbits 4 weeks after they were subjected to partial splenectomy using microwave tissue coagulation (PSM) group and to sham operation (SO groups), respectively. India ink was given via portal vein. Residual spleen were resected and microscopic examinations were performed on spleen slices stained using HE to compare phagocytic functions of macrophage. Gradings of phagocytic function in macrophage were of no significant difference between PSM and SO groups (P > 0.05). Weights of spleens showed no significant difference between the two groups (P > 0.05). The phagocytic function of macrophage after PSM can be preserved well. The result of this experiment implies that splenic salvage using MTC is a clinically applicable method.
Animals ; Female ; Macrophages ; immunology ; Male ; Microwaves ; therapeutic use ; Phagocytes ; immunology ; Rabbits ; Regeneration ; immunology ; Spleen ; physiology ; Splenectomy ; methods

Tumor immunology embraces an extensive array of biological phenomena that include interactions between neoplastic cells and the innate and adaptive immune response. Among immune cells, T cells have taken the center stage because they can be easily demonstrated to specifically recognize autologous cancer cells. However, their role is limited and other components of the immune response are likely necessary for the completion of cancer rejection. Metastatic melanoma and renal cell carcinoma (RCC) are malignancies strongly predisposed to regress in response to the systemic administration of high-dose interleukin (IL)-2. Several clinical Studies in extensive cohorts of patients have shown that this treatment can induce complete or partial clinical regressions of metastatic disease in 15 to 20% of patients who receive this treatment.1-6 Although IL-2 has direct pluri-potent effects on cells with immune and inflammatory function, it remains unexplained which cell subset is implicated in mediating tumor regression. In a quest to characterize the mechanism of action of IL-2 during the course of immunotherapy, we have investigated the early changes in transcriptional profiles of circulating mononuclear cells and microenvironment of melanoma metastases following high dose IL-2 administration (720,000 IU/kg) by serial sampling of blood cells and tumors in the form of fine needle aspirate (FNA).7 Furthermore, studies are currently ongoing to characterize the proteomic profiling of RCC patients undergoing the same treatment using protein arrays (manuscript in preparation). The predominant activation of genes related to inflammation and activation of mononuclear phagocytes lead us to further characterize this cell subset in the context of stimulation with a panel of soluble factors potentially present in the circulation and tumor microenvironment.
Antibody Formation ; Carcinoma, Renal Cell/metabolism/*therapy ; Gene Expression Profiling ; Humans ; *Immunotherapy ; Interleukin-2/*immunology/*therapeutic use ; Lipopolysaccharides/pharmacology ; Melanoma/genetics/immunology/secondary/*therapy ; Phagocytes/drug effects/physiology ; Proteomics

OBJECTIVETo review and summarize literature regarding stimulatory and inhibitory signaling pathways from different types of Fc gamma receptors (FcgammaRs).

DATA SOURCEArticles were obtained from Medline from January 1991 to April 2002.

STUDY SELECTIONOver 100 English language papers and reviews published over the last 11 years were selected.

RESULTS AND CONCLUSIONSStimulatory Fcgamma receptors include FcgammaRI, FcgammaRIIA, FcgammaRIIC, and FcgammaRIII A. They transduce signals through the immunoreceptor tyrosine-based activation motif (ITAM) in subunits or in the cytoplasmic domain. Inhibitory Fcgamma receptors, such as FcgammaRIIB, are single chain receptors, transducing signals through an immunoreceptor tyrosine-based inhibitory motif (ITIM) in cytoplasmic domains. Stimulatory signals include protein phosphorylation, increase in intracellular free calcium, the production of 1,4,5-triphosphate inositol (IP(3)) and diacylglycerol (DAG) mainly through the Src-family kinases, phosphoinositide 3-kinase (PI3-K) and phospholipase C (PLC). Inhibitory signaling has been implicated in the repression of the above activities as well as inhibition of B cell responses through Src homology 2-containing inositol phosphatase (SHIP).

Amino Acid Motifs ; Animals ; Blood Platelets ; physiology ; Humans ; Phagocytes ; physiology ; Receptors, IgG ; chemistry ; physiology ; Signal Transduction ; physiology