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Query: UNIPROT:P17931 (galectin-3)
2,860 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

IgE-binding protein (epsilon BP) is a galactoside-specific lectin containing an S-type carbohydrate-recognition domain. It was originally identified in rat basophilic leukemia cells and is now known to be identical to a macrophage surface Ag, Mac-2, and lectins designated as CBP 35/L-34/RL-29. It has also been related to a nonintegrin laminin-binding protein isolated from mouse macrophages. In this report we have shown the following: epsilon BP is present in variable amounts in several mast cell lines, and the surface expression of epsilon BP in these cell lines is quite variable and does not correlate with the total amount of epsilon BP in the cell. epsilon BP is displayed on the cell surface in a manner that is reversible by lactose, most likely through attachment to yet unidentified glycoconjugates. The putative epsilon BP binding sites on the cell surface can be readily demonstrated by using radiolabeled epsilon BP, and the sites are present in comparable amounts in various cell lines. Expression of epsilon BP on the cell surface can be regulated; the most notable example is the upregulation of surface epsilon BP on RBL cells activated through the high-affinity IgE receptor by IgE immune complexes. Cell-surface epsilon BP is functional as measured by its ability to promote adhesion of trypsinized rabbit erythrocytes to mast cells and macrophages. On the basis of these results and reported properties of related lectins, we propose that the lectin represented by epsilon BP is a new class of cell-adhesion protein.
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PMID:Surface expression of functional IgE binding protein, an endogenous lectin, on mast cells and macrophages. 173 Aug 78

IgE-binding protein (epsilon BP) refers to a protein originally identified in rat basophilic leukemia cells by virtue of its affinity for IgE. It is now known to be a beta-galactoside-binding lectin equivalent to carbohydrate-binding protein 35 (CBP 35). More recently, its identity to Mac-2, a macrophage cell-surface protein, has been established. cDNA coding for human epsilon BP has been cloned from a human HeLa cell cDNA library and contains an open reading frame of 750 base pairs encoding a 250 amino acid protein. Like the rat and murine counterparts, the human epsilon BP amino acid sequence can be divided into two domains with the amino-terminal domain consisting of a highly conserved repetitive sequence (YPGXXXPGA) and the carboxyl-terminal domain containing sequences shared by other S-type lectins. The human epsilon BP sequence exhibits extensive homology to murine and rat epsilon BP with 84% and 82% identity, respectively. The homology is particularly striking in the carboxyl-terminal domain where 95% identity is found between human and murine sequences in a stretch of over 70 amino acids. A survey of epsilon BP mRNA expression from several lymphocyte cell lines revealed that the level of epsilon BP transcription may reflect a relationship between cell differentiation and epsilon BP expression. Finally, human epsilon BP was purified from several human cell lines and shown to possess lactose-binding characteristics and cross-species reactivity to murine IgE. Surprisingly, three different human myeloma IgE proteins did not show reactivity to human epsilon BP. However, after neuraminidase treatment of each human IgE, pronounced binding to epsilon BP was observed, thereby indicating that only specific IgE glycoforms can be recognized by epsilon BP.
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PMID:Human IgE-binding protein: a soluble lectin exhibiting a highly conserved interspecies sequence and differential recognition of IgE glycoforms. 226 64

In N mice, peripheral nerve injury is followed by the normal rapid progression of Wallerian degeneration: Schwann cells proliferate and lose their myelin, which is phagocytized and metabolized by blood-borne macrophages. The role of Schwann cells in myelin phagocytosis is debated. Additionally, the molecular mechanisms underlying myelin phagocytosis by the two cell types are not well understood. To elucidate the role of Schwann cells as phagocytes we studied, electron microscopically, in vivo and in vitro degenerating, frozen, and neuroma nerve segments. The major cell types composing these tissues differed: Schwann and macrophages in in vivo degenerating; Schwann in in vitro degenerating; macrophages in frozen; Schwann, macrophages, and fibroblasts in neuroma nerve segments. Both macrophages and Schwann cells phagocytized myelin. We further studied, by immunocytochemistry and immunoblot analysis, the expression of molecules that are characteristically displayed by inflammatory and mature murine macrophages: MAC-1 (the C3b complement receptor), MAC-2 (a galactose-specific lectin), the Fc receptor, and the F4/80 antigen. All were detected in the macrophage-rich, in vivo degenerating, frozen, and neuroma nerve segments. Surprisingly, MAC-2 was also expressed in the macrophage-scarce, Schwann-rich, in vitro degenerating nerve. Immunocytochemistry and immunoblot analysis of isolated non-neuronal cells revealed that both macrophages and Schwann cells displayed MAC-2 on their surface and in their cytoplasm. Morphometry unveiled that galactose and lactose specifically inhibited myelin phagocytosis, as predicted if MAC-2 was mediating myelin phagocytosis by lectinophagocytosis (lectin-mediated phagocytosis). The role of MAC-2 in mediating myelin phagocytosis was further supported by two observations made in W mice that display very slow progression of Wallerian degeneration. First, the failure to degenerate in vivo was associated with deficient MAC-2 production. Second, degeneration that occurred in vitro was associated with MAC-2 production. Furthermore, a strong positive correlation between levels of MAC-2 expression and the extent of myelin destruction by phagocytosis was observed over a wide range of values.
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PMID:Peripheral nerve injury induces Schwann cells to express two macrophage phenotypes: phagocytosis and the galactose-specific lectin MAC-2. 818 68

Peripheral nerve injury is followed by Wallerian degeneration which is characterized by cellular and molecular events that turn the degenerating nerve into a tissue that supports nerve regeneration. One of these is the removal, by phagocytosis, of myelin that contains molecules which inhibit regeneration. We have recently documented that the scavenger macrophage and Schwann cells express the galactose-specific lectin MAC-2 which is significant to myelin phagocytosis. In the present study we provide evidence for a mechanism leading to the augmented expression of cell surface MAC-2. Nerve lesion causes noneuronal cells, primarily fibroblasts, to produce the cytokine granulocyte macrophage-colony stimulating factor (GM-CSF). In turn, GM-CSF induces Schwann cells and macrophages to up-regulate surface expression of MAC-2. The proposed mechanism is based on the following novel observations. GM-CSF mRNA was detected by PCR in in vitro and in vivo degenerating nerves, but not in intact nerves. The GM-CSF molecule was detected by ELISA in medium conditioned by in vitro and in vivo degenerating peripheral nerves as of the 4th h after injury. GM-CSF activity was demonstrated by two independent bioassays, and repressed by activity blocking antibodies. Significant levels of GM-CSF were produced by nerve derived fibroblasts, but neither by Schwann cells nor by nerve derived macrophages. Mouse rGM-CSF enhanced MAC-2 production in nerve explants, and up-regulated cell surface expression of MAC-2 by Schwann cells and macrophages. Interleukin-1 beta up-regulated GM-CSF production thus suggesting that injury induced GM-CSF production may be mediated by interleukin-1 beta. Our findings highlight the fact that fibroblasts, by producing GM-CSF and thereby affecting macrophage and Schwann function, play a significant role in the cascade of molecular events and cellular interactions of Wallerian degeneration.
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PMID:Granulocyte macrophage colony stimulating factor produced in lesioned peripheral nerves induces the up-regulation of cell surface expression of MAC-2 by macrophages and Schwann cells. 860 5

Knowledge of the number and kinds of differentiation steps characterizing cells of the osteoblast lineage is inadequate. To analyze further osteoblast differentiation, a number of labs have generated monoclonal antibodies to osteogenic cells, derived from both normal bone and osteosarcomas. A variety of immunolabelling patterns on primary cell cultures, cell lines, and tissue sections has been reported, including cell surface, cytoplasmic, and extracellular matrix-associated patterns. Most of the antibodies selected recognize predominantly the mature osteoblast and osteocyte; in addition, however, antibodies have been generated that recognize pre-osteoblasts. Some recognize cells of both the osteoblast and chondroblast lineages and may contribute to a better understanding of the lineage and phenotypic relationships between these two cell types. In addition to recognition in vivo of cell subpopulations of discrete maturational stages, changes in the immunolabelling patterns in vitro have also documented a differentiation sequence in cells undergoing osteogenesis in cell and tissue cultures. In at least two cases, the antibodies have been used to isolate subpopulations of cells from bone, including relatively pure populations of osteocytes. With the exception of several antibodies that are against alkaline phosphatase or known matrix proteins including osteocalcin, the nature of the macromolecular species recognized by most of the antibodies generated to date are unknown. Recently, however, one antibody was used to clone the cDNA for the beta-galactoside-binding lectin, galectin 3 or epsilon binding protein (epsilon BP; IgE-binding protein; Mac-2), from a lambda gt11 osteoblast expression library; another was used to clone from an ROS 17/2.8-COS cell expression library the cDNA for OTS-8, a putative target gene of early response genes stimulated in response to phorbol esters in MC3T3-E1 cells. Neither of these macromolecules had previously been identified in bone cells, but the recent molecular and cellular analyses have shown them to be developmentally and/or hormonally regulated in osteoblastic cells. These antibodies extend the available markers and support earlier observations that a variety of molecules are differentially expressed by cells at different stages of the osteoblast lineage. This chapter will not be an exhaustive survey of all immunocytochemical and immunohistochemical analyses of osteogenic cells and tissues but will focus on the approach of eliciting novel monoclonal antibodies by the injection of osteogenic cells or crude bone extracts and its potential for establishing new markers of the osteoblast lineage. We have not included a large number of studies documenting the use of antibodies raised against several known bone matrix proteins; while these have been crucial in developing our current understanding of osteogenic differentiation, we sought rather to highlight the potential of the "random" injection approach.
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PMID:Monoclonal antibodies as tools for studying the osteoblast lineage. 884 13

Galectin 3 is an endogenous soluble beta-galactoside-specific lectin originally identified and termed epsilon BP or IgE-binding protein in rat basophilic leukemia cells, but its wide tissue distribution and the multiple contexts in which it has been isolated have suggested that its function may not be limited to IgE binding but may include a role in cell growth regulation and differentiation, neoplastic transformation, and cell adhesion (Liu, 1990, Crit. Rev. Immunol., 10:289-306; Barondes et al., 1994, J. Biol. Chem., 269:20807-20810). After immunoscreening of a lambda gt11 cDNA expression library made from bone-nodule forming cultures of fetal rat calvaria (RC) cells with an antibody raised against osteoblastic cells (Turksen et al., 1992, J. Histochem. Cytochem., 40:1339-1352), three cDNA clones were isolated and sequenced; the sequence matched that of rat galectin 3. Galectin 3 mRNA was detected in various fetal and adult rat tissues, including calvaria and cultured RC cells. In RC cells and the rat osteosarcoma cell line ROS 17/2.8, galectin 3 mRNA expression increased with time in culture, in contrast to its behavior in fetal rat skin fibroblasts (RSF) in which its expression decreased with time in culture. In a second rat osteosarcoma line, UMR 106.01, galectin 3 mRNA was almost nondetectable. The synthetic glucocorticoid dexamethasone (Dex) enhanced galectin 3 expression in RSF cell cultures, while 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) had no significant effect. In contrast, Dex downregulated and 1,25(OH)2D3 upregulated galectin 3 expression in RC and ROS 17/2.8 cells, especially at later time points in culture when expression of osteoblast-associated differentiation markers by these cell types is most marked. Immunolabeling with an antibody against rat galectin 3 to identify galectin 3 protein showed that cells labelled within both the ROS 17/2.8 and RC populations but with marked intercellular heterogeneity of intensity. Our data support the conclusion that galectin 3 is a previously unrecognized product of osteoblastic cells, that galectin 3 mRNA and protein expression increases with time in vitro concomitant with other markers of osteogenesis, including formation of bone nodules and expression of osteoblast-associated markers such as alkaline phosphatase, bone sialo-protein, and osteocalcin, and that its expression is regulated by hormones such as glucocorticoids and 1,25(OH)2D3 that modulate other aspects of the osteoblast phenotype.
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PMID:Expression and regulation of galectin 3 in rat osteoblastic cells. 895 96

Reactivity of the N-acetylgalactosamine-binding Helix pomatia agglutinin (HPA) in tumours has been associated with poor prognosis and metastasis development. In our LOX/FEMX-I human melanoma model, the binding of HPA correlates with experimental lung metastasis formation in athymic nude mice. In the present study, the metastatic potential of 2 human melanoma cell lines (LOX and FEMX-I) was assessed in relation to carbohydrate and invasive phenotype. Immunocytological and invasion assays highlighted significant differences between these 2 cell lines. Immuno-cytochemical analysis confirmed the widespread expression of HPA-binding glycoconjugates on LOX but not FEMX-I cells. One of these HPA-binding glycoconjugates, the Tn antigen, was expressed highly on the surface of LOX cells but only weakly in the cytoplasm of FEMX-I cells. The sialyl Tn antigen was expressed in FEMX-I but not in LOX cells. There was no difference between the cell lines in adhesion/rate of trapping in athymic nude mouse lung tissues. In Matrigel invasion assays, LOX cells demonstrated an invasion potential more than 6 times greater than that observed with FEMX-I cells. Matrigel invasion of LOX cells was inhibited after incubation with HPA (89%) compared to controls with HPA and GalNAc blocking sugar or without HPA (p < 0.0005 at 5 df). In contrast, there was no inhibitory effect with the anti-Tn antibody IE3. Invasion of FEMX-I cells was not affected by the lectin and the IE3 antibody. Immuno-cytochemical analysis revealed expression of the terminal galactose- and polylactosamine-binding lectin galectin 3 (Mac-2) in these melanoma cell lines. Expression of both the lectin and its receptor may be a contributory feature in the pulmonary invasion of LOX melanoma cells. Overall, our findings suggest that HPA-binding glycoconjugates other than the alphaGalNAc-O-Ser/Thr of the Tn antigen may be important in the extracellular matrix invasion of LOX melanoma cells.
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PMID:Invasion potential and N-acetylgalactosamine expression in a human melanoma model. 946 64

Wallerian degeneration (WD) is the inflammatory response of peripheral nerves to injury. Evidence is provided that granulocyte macrophage colony stimulating factor (GM-CSF) contributes to the initiation and progression of WD by activating macrophages and Schwann, whereas IL-10 down-regulates WD by inhibiting GM-CSF production. A significant role of activated macrophages and Schwann for future regeneration is myelin removal by phagocytosis and degradation. We studied the timing and magnitude of GM-CSF and IL-10 production, macrophage and Schwann activation, and myelin degradation in C57BL/6NHSD and C57BL/6-WLD/OLA/NHSD mice that display normal rapid-WD and abnormal slow-WD, respectively. We observed the following events in rapid-WD. The onset of GM-CSF production is within 5 h after injury. Production is steadily augmented during the first 3 days, but is attenuated thereafter. The onset of production of the macrophage and Schwann activation marker Galectin-3/MAC-2 succeeds that of GM-CSF. Galectin-3/MAC-2 production is up-regulated during the first 6 days, but is down-regulated thereafter. The onset of myelin degradation succeeds that of Galectin-3/MAC-2, and is almost complete within 1 week. IL-10 production displays two phases. An immediate low followed by a high that begins on the fourth day, reaching highest levels on the seventh. The timing and magnitude of GM-CSF production thus enable the rapid activation of macrophages and Schwann that consequently phagocytose and degrade myelin. The timing and magnitude of IL-10 production suggest a role in down-regulating WD after myelin is removed. In contrast, slow-WD nerves produce low inefficient levels of GM-CSF and IL-10 throughout. Therefore, deficient IL-10 levels cannot account for inefficient GM-CSF production, whereas deficient GM-CSF levels may account, in part, for slow-WD.
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PMID:The cytokine network of wallerian degeneration: IL-10 and GM-CSF. 976

The removal of degenerating myelin by phagocytosis is central to pathogenesis and repair in traumatized and diseased nervous system. Galectin-3/MAC-2 is a differentiation and activation marker of murine and human monocytes/macrophages/microglia. Galectin-3/MAC-2, along with MAC-1 that mediates myelin phagocytosis, marks an in vivo activation state in macrophages, which are involved in myelin degeneration and phagocytosis in injured mouse peripheral nerves. In contrast, high levels of MAC-1 but extremely low levels of Galectin-3/MAC-2 are expressed in vivo in injured CNS where myelin degeneration and phagocytosis progress extremely slowly. The present study was aimed at testing whether an activation state marked by Galectin-3/MAC-2 is present in vivo in the CNS of EAE mice concomitant with autoimmune induced myelin degeneration and phagocytosis. EAE was inflicted by mouse spinal cord homogenate. Demyelination was assessed by light microscopy and Galectin-3/MAC-2, MAC-1, and F4/80 expression by immunocytochemistry. We presently document that Galectin-3/MAC-2 expression is up regulated, along with MAC-1 and F4/80, in spinal cords and optic nerves of EAE mice in areas of demyelination and myelin degeneration, in myelin phagocytosing microglia and macrophages. Copolymer 1 (Glatiramer acetate) suppresses EAE, demyelination, and Galectin-3/MAC-2 expression. EAE pathogenesis thus involves a state of activation in microglia and macrophages characterized by the expression Galectin-3/MAC-2 along with MAC-1. Furthermore, the in vivo responses to injury and autoimmune challenge in the CNS differ in the activation pattern of microglia and macrophages with regard to Galectin-3/MAC-2 expression and the corresponding occurrence of myelin degeneration and phagocytosis.
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PMID:Galectin-3/MAC-2 in experimental allergic encephalomyelitis. 1061 68

Galectin-3, a member of a family of carbohydrate-binding proteins, is present generally in the cytoplasm of cells. However, galectin 3 can also be located in nuclei under certain conditions although it lacks any known nuclear localisation signal and the mechanism by which the protein is sequestered in nuclei is unknown. Here we describe that Cos-7 cells or rabbit smooth muscle Rb-1 cells transfected with cDNA encoding hamster galectin-3 sequester the protein in nuclei whereas untransfected BHK cells expressing the endogenous hamster lectin or transfected BHK cells over-expressing the protein, do not. Confocal immunofluorescence microscopy of Cos-7 cells or rabbit smooth muscle Rb-1 cells transfected with cDNAs encoding mutants of hamster galectin-3 containing N-terminal or internal deletions shows that nuclear localisation does not require the first 103 amino acid residues of the protein. Further deletion of residues 104-110 dramatically prevents sequestration in nuclei. However, the sequence A104PTGALT110 by itself is not obligatory for nuclear localisation and can be substituted by other unrelated sequences. A truncated galectin-3 protein, that is blocked in nuclear expression, retains carbohydrate-binding activity, making less likely the possibility that severe N-terminal truncations of galectin-3 induce mis-folding leading to aggregation and cytoplasmic sequestration and an incidental effect on nuclear trafficking. These studies indicate that nuclear import and retention of galectin-3 is a property of the CRD domain and is independent of N-terminal domains that others have shown to contain binding domains for various nuclear components.
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PMID:Nuclear localisation of wild type and mutant galectin-3 in transfected cells. 1076 97

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