Remodeling of the mitochondrial network is an important process in the maintenance of cellular homeostasis and is closely related to mitochondrial function. Interactions between the biogenesis of new mitochondria and the clearance of damaged mitochondria (mitophagy) is an important manifestation of mitochondrial network remodeling. Mitochondrial fission and fusion act as a bridge between biogenesis and mitophagy. In recent years, the importance of these processes has been described in a variety of tissues and cell types and under a variety of conditions. For example, robust remodeling of the mitochondrial network has been reported during the polarization and effector function of macrophages. Previous studies have also revealed the important role of mitochondrial morphological structure and metabolic changes in regulating the function of macrophages. Therefore, the processes that regulate remodeling of the mitochondrial network also play a crucial role in the immune response of macrophages. In this paper, we focus on the molecular mechanisms of mitochondrial regeneration, fission, fusion, and mitophagy in the process of mitochondrial network remodeling, and integrate these mechanisms to investigate their biological roles in macrophage polarization, inflammasome activation, and efferocytosis.
Mitochondria ; Mitophagy ; Homeostasis/physiology* ; Phagocytosis ; Macrophages/metabolism*

The aim of this study was to investigate the effects of polarization program on the ability of macrophages to regulate iron metabolism. M1 and M2 macrophages were propagated in vitro from porcine alveolar macrophages 3D4/2 and polarized by cytokines. The 3D4/2 macrophages were treated with 20 ng/mL interferon gamma (IFN-γ) and 10 ng/mL interleukin-4 (IL-4) combined with 10 ng/mL macrophage colony-stimulating factor (M-CSF) to induce polarization to M1 and M2, respectively. After incubation for 24 h, the expression levels of inflammatory factors and iron-metabolism genes were determined using real-time qPCR, Western bot and immunofluorescence. The M1/M2 macrophages culture media supernatant was collected and used to treat porcine intestinal epithelial cells IPEC-J2. The proliferation ability of IPEC-J2 was detected using CCK-8 assay kit. Following exogenous addition of ammonium ferric citrate (FAC) to M1/M2 macrophages, the phagocytic function of macrophages was detected using fluorescein isothiocyanate-dextran (FITC-dextran) and flow cytometry. The results showed that, compared with control, M1 macrophages had higher mRNA levels of iron storage proteins (ferritin heavy and light polypeptide, i.e. FtH and FtL), hepcidin and lipocalin-2, as well as iron content. Moreover, iron enhanced the ability of M1 macrophages to phagocytize FITC-dextran. There was no significant change in these mRNA expression levels in M2 macrophages, but the mRNA expression levels of ferroportin and transferrin receptor were up-regulated. In addition, the conditioned media supernatant from M2 macrophages promoted cell proliferation of IPEC-J2. These findings indicate that M1 macrophages tend to lock iron in the cell and reduce extracellular iron content, thereby inhibiting the proliferation of extracellular bacteria. While M2 macrophages tend to excrete iron, which contributes to the proliferation of surrounding cells and thus promotes tissue repair.
Animals ; Cytokines ; Ferritins ; Iron/metabolism* ; Macrophages/metabolism* ; Macrophages, Alveolar/metabolism* ; Swine

Objective To investigate the molecular mechanism of taurine regulating the polarization of M2 macrophages by mitophagy. Methods THP-1 cells were divided into four groups: M0 group (THP-1 cells were treated by 100 nmol/L phorbol myristate ester for 48 hours to polarize into M0), M2 group (THP-1 cells were induced to polarize into M2 macrophages by 20 ng/mL interferon-4 (IL-4) for 48 hours), M2 combined with taurine groups (added with 40 or 80 mmol/L taurine on the basis of M2 macrophages). The mRNA expression of mannose receptor C type 1(MRC-1), C-C motif chemokine ligand 22(CCL22) and dendritic cell-specific ICAM-3 grabbing non-integrin (CD209) in M2 macrophages were detected by quantitative real-time PCR. Mitochondrial and lysosome probes were used to detect the number of mitochondria and lysosomes by multifunction microplate reader and confocal laser scanning microscope. The level of mitochondrial membrane potential (MMP) was detected by JC-1 MMP assay kit. The expression of mitophagy-related proteins PTEN-induced putative kinase 1 (PINK1) and microtubule-associated protein 1 light chain 3 (LC3) were detected by Western blot analysis. Results Compared with M0 group, the expression of MRC-1, CCL22, CD209 and PINK1, the number of mitochondria and the level of MMP in M2 group were significantly increased, whereas the number of lysosomes and LC3II/LC3I ratio were decreased. Compared with M2 group, the expressions of MRC-1, CCL22 and CD209, the number of mitochondria and the level of MMP in M2 combined with taurine group dropped significantly while the number of lysosomes was found increased, and the protein expression of PINK1 and LC3II/LC3I ratio were also increased. Conclusions The polarization of M2 macrophages is regulated by taurine to prevent excessive polarization via reducing the level of MMP, improving the level of mitophagy, reducing the number of mitochondria, and inhibiting the mRNA expression of polarization markers in M2 macrophages.
Mitophagy ; Taurine ; Macrophages/metabolism* ; Protein Kinases/metabolism* ; RNA, Messenger

Recently it is known that nitric oxide(NO) generated by an activatedmacrophage plays an important role in tumoricidal or bactericidal activity. Thisstudy was done to know the effects of NO produced by the activated macrophages onthe growth of the murine bladder tumor cell line (MBT-2). For the activation ofmacrophages, RAW 264.7 cell line ( macrophage-derived cell line) and peritonealmacrophages from Balb/c mouse were treated with interferon-r (INF-r),lipopolysaccharide ( LPS) or INF-r plus LPS and for the evaluation of growthinhibition of MBT -2 cell line, tritiated thymidine (3[H] -thymidine)incorporation was measured after coculturing of MBT-2 cell line with macrophageswhich had been activated to produce NO. The results are as follows : l.Peritoneal macrophages from Balb/c mouse could be activated to produce NO onlywhen they are stimulated by the combination of INF-r and LPS (35+/-1.0uM/L). Theycould produce a slight increase amount of NO when they had been stimulated byINF-r (11+/-2.5uM/ L) or LPS (14+/-3.5uM/L) compared to control macrophages(8+/-2.5uM/L). The induction of NO production by INF-r plus LPS could be abrogatedby the use of NG-monomethyl-L- arginine (NGMMA), a competitive inhibitor of NOsynthase (5+/-1.5 M/L). 2. RAW 264.7 cell lines could be activated to produce NOby the treatment of INF-r, LPS, and INF-r plus LPS (40+/-2.5uM/L, 37+/-3.0uM/Land 51+/-2.6uM/L respectively). When they are treated with NGMMA, they produced nomore NO even though they had been stimulated with INF-r plus LPS (14+/-4.0uM/L),and they could produce small .amount of NO(19+/-1.0uM/L) in the absence of thestimulation. 3. The incorporation of 3[H] -thymidine of the MBT-2 and peritonealmacrophages was reduced when the cells had been treated with INF-r plus LPScompared to the control (14,519+/-1,087cpm, 20,716+/-1,474cpm respectively).There was no reduction in the incorporation of 3[H] -thymidine when the cellshad been treated with INF-r or LPS alone. The incorporation of 3[H]-thymidineincreased when the cells had been treated with INF-r plus LPS in the presence ofNGMMA(19,622+/-1,341cpm). 4. The incorporation of 3[H] -thymidine of the MBT-2 and RAW 264.7 cell lines were reduced when the cells had been treated with INF-r, LPS and INF-r plus LPS (19.068+/-144cpm, 15,070+/-122cpm and 7,543+/-85cpm respectively) compared to control( 20,708+/-142cpm). When the cells had been pretreated with NGMMA, the incorporation of 3[H]- thymidine recovered to same degree (12,605+/-108cpm) compared to the cells stimulated with INF-r plus LPS. The above correlation of the NO production from macrophages which had been stimulated by INF-r and/or LPS and the inhibition of growth of the tumor cells suggests that NO produced by stimulated macrophages might be the responsible molecule in the defense system of the body against tumors.
Animals ; Arginine ; Cell Line* ; Macrophages* ; Macrophages, Peritoneal ; Metabolism* ; Mice ; Nitric Oxide ; Nitrogen* ; Thymidine ; Urinary Bladder Neoplasms

Atherosclerosis (AS) is an invisible killer among cardiovascular diseases (CVD), which has seriously threatened the life of quality. The complex pathogenesis of AS involves multiple interrelated events and cell types, such as macrophages, endothelial cells, vascular smooth muscle cells and immune cells. Currently, the efficacy of recommended statin treatment is not satisfactory. Natural products (NPs) have attracted increasing attention with regard to their broad structural diversity and biodiversity, which makes them a promising library in the demand for lead compounds with cardiovascular protective bio-activity. NPs can preclude the development of AS by regulating lipid metabolism, ameliorating inflammation, stabilizing plaques, and remodeling the gut microbiota, which lays a foundation for the application of NPs in clinical therapeutics.
Humans ; Biological Products/metabolism* ; Endothelial Cells/metabolism* ; Atherosclerosis/metabolism* ; Macrophages/metabolism* ; Inflammation/metabolism*

OBJECTIVETo investigate the expression of cytokines induced by Actinobacillus actinomycetemcomitans lipopolysaccharide (Aa-LPS) in monocytes/macrophages from different organs of rabbits.

METHODSThe peripheral mononuclear cells (Mo), alveolar macrophages (AM), peritoneal macrophages (PM) and Kupffer cells (KC) from five New Zealand rabbits were isolated respectively. Then the cells from different organs were stimulated with Escherichia coli (Ec)-LPS or Aa-LPS at the dose of 1 mg/L. After culture for 24 hours, the expression of tumor necrosis factor-α (TNF-α), interleukin (IL)6, IL-1β, IL-8 mRNA and protein were determined by real-time PCR and enzyme-linked immunosorbent assay respectively.

RESULTSThe monocytes/macrophages challenged by Ec-LPS or Aa-LPS expressed more cytokines both in mRNA and protein levels compared with the controls (P < 0.05). Among them, AM displayed the highest respond when encount with Aa-LPS, with the TNF-α, IL-6, IL-1β, IL-8 mRNA relative levels were (0.4719 ± 0.0171), (2.7895 ± 0.0669), (5.1527 ± 0.1190), (3.6785 ± 0.1836) and the proteins concentrations were (82.2 ± 5.4), (40.2 ± 2.0), (50 308.3 ± 445.0), (35 305.3 ± 1480.9) ng/L respectively. And the inducibility of Aa-LPS was stronger than that of Ec-LPS (P < 0.05). Meanwhile the cells from different organs showed discrepant response when exposed to Aa-LPS (P < 0.05). The results showed their abilities to secrete cytokines were in the sequence of AM > Mo > KC > PM.

CONCLUSIONSAa-LPS influenced the expression of cytokines in monocytes/macrophages from different organs of rabbits.

Aggregatibacter actinomycetemcomitans ; Animals ; Cells, Cultured ; Interleukin-1beta ; metabolism ; Interleukin-6 ; metabolism ; Interleukin-8 ; metabolism ; Lipopolysaccharides ; adverse effects ; Macrophages ; metabolism ; Macrophages, Alveolar ; metabolism ; Macrophages, Peritoneal ; metabolism ; Monocytes ; metabolism ; RNA, Messenger ; genetics ; Rabbits ; Tumor Necrosis Factor-alpha ; metabolism

CD47, also known as integrin-associated protein (IAP), is an immunoglobulin-like protein. It can inhibit the phagocytosis of macrophages through binding with signal-regulatory protein alpha chain of inhibitory receptor on macrophage (SIRPα). The expression of CD47 on normal hematopoietic stem cells (HSCs) is useful for maintaining the stability of HSCs in body, but the high expression of CD47 existed on leukemia stem cell (LSCs) of AML patients which can reduce the macrophage-induced phagocytosis to LSCs and decrease the clearance of innate immune system of organism to LSCs. In this article, the expression and function of CD47 on HSCs and LSCs as well as the role of CD47 in the prognosis and target therapy of AML are reviewed.
CD47 Antigen ; metabolism ; Humans ; Leukemia ; metabolism ; Macrophages ; metabolism ; Neoplastic Stem Cells ; metabolism ; Phagocytosis

High mobility group box 1 (HMGB1) is an evolutionarily conserved non-histone chromatin-binding protein. During infection or injury, activated immune cells and damaged cells release HMGB1 into the extracellular space, where HMGB1 functions as a proinflammatory mediator and contributes importantly to the pathogenesis of inflammatory diseases. Recent studies reveal that inflammasomes, intracellular protein complexes, critically regulate HMGB1 release from activated immune cells in response to a variety of exogenous and endogenous danger signals. Double stranded RNA dependent kinase (PKR), an intracellular danger-sensing molecule, physically interacts with inflammasome components and is important for inflammasome activation and HMGB1 release. Together, these studies not only unravel novel mechanisms of HMGB1 release during inflammation, but also provide potential therapeutic targets to treat HMGB1-related inflammatory diseases.
HMGB1 Protein ; chemistry ; metabolism ; Humans ; Inflammasomes ; metabolism ; Macrophages ; immunology ; metabolism ; eIF-2 Kinase ; metabolism

Macrophages have been shown to have pleiotropic functions in various pathophysiologies, especially in terms of anti-inflammatory and regenerative activity. Recently, the novel functions of bone marrow resident macrophages (called osteal macrophages) were intensively studied in bone development, remodeling and tissue repair processes. This review discusses the current evidence for a role of osteal macrophages in bone modeling, remodeling, and fracture healing processes.
Bone Development ; Bone Marrow ; Bone Remodeling ; Fracture Healing ; Macrophages* ; Metabolism*

As a result of the stimulation of proinflammatory mediators, circulating peripheral-blood mononuclear cells migrate into the wound area, and they differentiate into different phenotypes of macrophage to take different roles in healing process. Their phenotypes interchange under different microenvironments. The disturbance of cutaneous environment in diabetic patients has been shown to alter the quantity, morphology, and functions of the macrophages resulting in retardation of wound healing. Healing of intractable diabetic wound can be improved by the supplement of exogenous growth factors, which might improve healing process by regulating the phenotype of macrophage in intractable diabetic wound. This article reviews the relationship between intractable diabetic wound and macrophage to explore new methods of treating intractable diabetic wound.
Diabetes Mellitus ; immunology ; metabolism ; Humans ; Macrophages ; physiology ; Skin ; Wound Healing