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

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

Fungi immunoregulatory proteins family is effective in immunological regulation and anti-tumor. We used Pichia pastoris expression system for recombinant expression of Lz-8, an immunomodulatory protein isolated from fruiting body of Ganoderma lucidum. The Gs115 (mut+) strains of P. pastoris was used as host cells. PCR and sequencing of DNA showed that Lz-8 cDNA was successfully integrated into the P. pastoris genome. Electrophoresis (SDS-PAGE), matrix assisted laser desorption ionisation time-of-flight mass spectrometry (MALDI-TOF-MS) and immunological techniques were used to identify recombinant Lz-8 (rLz-8). Lz-8 expressed in Escherichia coli, the Pichia system requires further optimization to obtain more active fungi immunomodulatory protein. Lz-8 was expressed in P. pastoris successfully, and polyacrylamide gel electrophoresis in the presence of SDS-PAGE gave a single band with an apparent Mr=14,000 D. MALDI-TOF-MS also showed that molecular weight of rLz-8 was 12,722 D. Aggregation was observed from sheep red blood cells in the presence of purified rLz-8 within the concentration range of 12.5-50 microg/mL. However, no aggregation was seen at concentration greater than 50 microg/mL for any type of human red blood cell. The dose at 0.5 mg/kg of rLz-8 induced macrophage cytophagocytesis, and set interferon as control at 0.5 mg/kg. These results suggested that active and stable rLz-8 was obtained in P. pastoris expression system.
Fungal Proteins ; biosynthesis ; genetics ; immunology ; Immunocompetence ; immunology ; Macrophages ; immunology ; Phagocytosis ; drug effects ; Pichia ; genetics ; metabolism ; Recombinant Proteins ; biosynthesis ; genetics ; immunology

Polysaccharides extracted from various sources are natural active substances, which may lead to the activation of macrophage via multiple pathways and mechanisms. This article intends to illustrate the signaling pathways of polysaccharides from plants, fungi, algae and other sources, to identify the mechanisms on the molecular level, and to explore the novel target immunomodulatory agents.
Animals ; Humans ; Macrophage Activation ; drug effects ; immunology ; Macrophages ; drug effects ; immunology ; metabolism ; Polysaccharides ; pharmacology ; Signal Transduction

The inflammasome is an emerging new pathway in innate immune defense against microbial infection or endogenous danger signals. The inflammasome stimulates activation of inflammatory caspases, mainly caspase-1. Caspase-1 activation is responsible for processing and secretion of IL-1β and IL-18 as well as for inducing macrophage pyroptotic death. Assembly of the large cytoplasmic inflammasome complex is thought to be mediated by members of NOD-like receptor (NLR) family. While functions of most of the NLR proteins remain to be defined, several NLR proteins including NLRC4 have been shown to assemble distinct inflammasome complexes. These inflammasome pathways, particularly the NLRC4 inflammasome, play a critical role in sensing and restricting diverse types of bacterial infections. Here we review recent advances in defining the exact bacterial ligands and the ligand-binding receptors involved in NLRC4 inflammasome activation. Implications of the discovery of the NAIP family of inflammasome receptors for bacterial flagellin and type III secretion apparatus on future inflammasome and bacterial infection studies are also discussed.
Animals ; Bacteria ; immunology ; Bacterial Infections ; immunology ; metabolism ; CARD Signaling Adaptor Proteins ; immunology ; metabolism ; Caspase 1 ; metabolism ; Flagellin ; immunology ; metabolism ; Humans ; Immunity, Innate ; immunology ; Macrophages ; immunology ; metabolism ; microbiology ; Neuronal Apoptosis-Inhibitory Protein ; immunology ; metabolism

OBJECTIVETo study the effect of the cultured supernatant of human silicotic alveolar macrophages (AM) on the expression of the collagen type I in human embryonic lung fibroblasts.

METHODSHuman alveolar macrophages were collected from a silicotic patient by bronchoalveolar lavage and exposed to silicon dioxide for 18 h. Then the cultured supernatant were used to culture human embryonic lung fibroblasts for 6 h, 12 h, 18 h, 24 h, 36 h, 48 h, 72 h. Then detected collagen anabolism and secretion with (3)H-proline detected the expression of the procollagen type I in the fibroblast with immunological method detected the quantity of collagen Type I in FB supernatant with Western blot.

RESULTSThe anabolism and secretion of collagen were increased in cultured supernatant of silicotic AM exposed to SiO(2), Along with the time, the expression of collagen type I increased. In cultured supernatant of silicotic AM exposed to SiO(2), ((3)H-proline: 1096.500 +/- 76.400, 707.000 +/- 62.160, OD: 0.314 +/- 0.011, OD: 14.218 +/- 0.342.

CONCLUSIONSiO(2) may affect the expression of collagen through AM mediation and participate in the formation of lung fibrosis.

Adult ; Cells, Cultured ; Collagen Type I ; metabolism ; Fibroblasts ; metabolism ; Humans ; Lung ; metabolism ; Macrophages, Alveolar ; immunology ; Male ; Silicosis ; immunology

Inhibition of macrophage-mediated phagocytosis has emerged as an essential mechanism for tumor immune evasion. One mechanism inhibiting the innate response is the presence of the macrophage inhibitory molecule, signal regulatory protein-α (SIRPα), on tumor-associated macrophages (TAMs) and its cognate ligand cluster of differentiation 47 (CD47) on tumor cells in the tumor microenvironment. On the basis of a recently discovered programmed death protein 1 (PD-1) in TAMs, we discuss the potential inhibitory receptors that possess new functions beyond T cell exhaustion in this review. As more and more immune receptors are found to be expressed on TAMs, the corresponding therapies may also stimulate macrophages for phagocytosis and thereby provide extra anti-tumor benefits in cancer therapy. Therefore, identification of biomarkers and combinatorial therapeutic strategies, have the potential to improve the efficacy and safety profiles of current immunotherapies.
Antigens, Surface ; metabolism ; Apoptosis Regulatory Proteins ; metabolism ; Humans ; Immunotherapy ; methods ; Macrophages ; immunology ; Neoplasms ; immunology ; pathology ; therapy ; Phagocytosis ; immunology ; Treatment Outcome ; Tumor Microenvironment ; immunology

OBJECTIVE: To investigate the distribution of pulmonary surfactant protein A (SP-A) like molecules and the bridge of frontier host defense and adaptive immune response cell of CD68 positive macrophages in inflammatory bowel disease (IBD). METHODS: Surgical specimens derived from involved areas and normal area of the colon with Crohn disease (CD) and ulcerative colitis (UC) were obtained from Department of Pathology, Rhode Island Hospital, Brown University Medical Center. The distribution of SP-A like molecule in intestine of IBD was detected by immunohistochemistry. RESULTS: SP-A like molecule located in epithelia of intestine, the surface of intestine villi, blood vessels of connective tissue, and some inflammatory cells. The number of macrophages with both SP-A like molecule and CD68 positive was dramatically increased in the inflammatory area than the normal area. Some CD68 positive macrophages expressed SP-A like immunoreactivity by immunofluorescence double labeling. CONCLUSION SP-A is an important host defense molecule in lung, and SP-A expression in large intestine may reflect a close relation between 2 organs in immune response towards inflammation.
Antigens, CD ; metabolism ; Antigens, Differentiation, Myelomonocytic ; metabolism ; Colitis, Ulcerative ; immunology ; metabolism ; Colon ; metabolism ; Crohn Disease ; immunology ; metabolism ; Humans ; Immunohistochemistry ; Inflammatory Bowel Diseases ; immunology ; metabolism ; Macrophages ; immunology ; metabolism ; Pulmonary Surfactant-Associated Proteins ; genetics ; metabolism

A primitive protozoan parasite Trichomonas vaginalis selectively activates the signal transduction pathways in macrophages (RAW264.7). This study evaluated the correlation of these signaling pathways and T. vaginalis-induced cell apoptosis. In macrophages infected with T. vaginalis, apoptosis was assessed on the basis of DNA fragmentation on agarose gel electrophoresis. Infection of macrophages with T. vaginalis induced tyrosine phosphorylation of several proteins. Infected cells with T. vaginalis were shown to associate with phosphorylation of the extracellular signal-regulated (ERK) 1/2 kinase, p38, c-Jun N-terminal kinase (JNK) mitogen-activated protein (MAP) kinases on Western blot analysis. The present finding also demonstrated a link between the ERK1/2, JNK and p38 apoptotic pathways that was modulated by T. vaginalis infection.
Animals ; Apoptosis/*immunology ; Humans ; MAP Kinase Signaling System/immunology ; Macrophages/*cytology/enzymology/*parasitology ; Mitogen-Activated Protein Kinases/*metabolism ; Phosphorylation ; Trichomonas Infections/*immunology ; Trichomonas vaginalis/*immunology

Phagocytosis of serum- and IgG-opsonized zymosan (SOZ and IOZ, respectively) particles into J774A.1 macrophages induced apoptosis of the cells, accompanied by the expression of p21(WAF1), one of cyclin-dependent protein kinase (CDK) inhibitors. Furthermore, phagocytosis of SOZ and IOZ particles into macophages induced superoxide formation. Tat-superoxide dismutase (SOD), which is readily transduced into the cells using Tat-domain, protected the cells from the apoptosis induced by phagocytosis of SOZ and IOZ particles. lipopolysaccharide (LPS)/interferon-gamma (IFN-gamma) also caused the apoptosis of the cells. However, Tat-SOD could not protect the cells from LPS/IFN-gamma induced apoptosis, suggesting that apoptosis mechanisms involved are different from each other. In the present study, we determined the amounts of nitric oxide (NO) produced by SOZ, IOZ, and LPS/IFN-gamma, and found that SOZ and IOZ did not induce the generation of NO in macrophages, whereas LPS/ IFN-gamma did. The apoptosis due to phagocytosis was accompanied with the release of cytochrome c from mitochondrial membrane to cytosolic fraction. Furthermore, SOZ and IOZ induced the cleavage of procasapase-3 (35 kDa) to give rise to an active caspase-3 (20 kDa), which was blocked by Tat- SOD but not by 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide (PTIO), a scavenger of NO. On the other hand, LPS/IFN-gamma caused the activation of procaspase-3, which was blocked by PTIO but not by Tat-SOD. Taken together, phagocytosis of SOZ and IOZ particles induced apoptosis through superoxide but not NO in macrophages, accompanied with the release of cytochrome c and the activation of caspase-3.
Apoptosis/*immunology ; Caspases/metabolism ; Cell Line ; Cyclins/biosynthesis ; Cytochromes c/metabolism ; Immunoglobulin G/*immunology ; Interferon Type II/pharmacology ; Lipopolysaccharides/pharmacology ; Macrophages/*immunology/metabolism ; Nitric Oxide/*metabolism ; Opsonins/immunology ; Phagocytosis/*physiology ; Superoxide Dismutase/metabolism ; Superoxides/*metabolism ; Zymosan