Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P17931 (galectin-3)
 2,860 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The binding of a membrane proteoglycan from a non-encapsulated strain of Klebsiella pneumoniae (Kp-MPG) and four derivatives thereof, to human leukocytes, was investigated by indirect immunofluorescence using biotinylated F(ab')2 fragments of anti-Kp-MPG antibodies and the streptavidin-phycoerythrin amplification system in flow cytometry. Four Kp-MPG derivatives were studied: 1/ an acylpoly(1,3)galactoside (APG), 2/ an APG preparation submitted to acid hydrolysis which removed all fatty acids, but left intact the galactose chain of APG (GC-APG), 3/ a preparation obtained by mild alkaline hydrolysis, containing additional ester-linked C14 and C16 fatty acids bound to the APG molecule (EFA-APG) and 4/ a polymer of the latter compound (APG pol). Kp-MPG, APG and EFA-APG were shown to bind exclusively to monocytes at the lowest concentrations (from 0.15 to 3 microM APG). At higher concentrations, these compounds interacted with polymorphonuclear leukocytes, and with lymphocyte subsets in the following decreasing order: B cells, NK cells, CD8+ and CD4+ lymphocytes. Neither APG pol or GC-APG nor K. pneumoniae smooth LPS showed significant binding to leukocytes. However Kp-LPS treated by drastic alkaline hydrolysis displayed binding properties similar to those of APG. Removal of the ester-linked C14 and C16 fatty acids from EFA-APG did not affect the binding of the molecule. The capacity of cells from the myelomonocytic lineage to bind Kp-MPG and APG was very low in phenotypically immature cell lines (HL60 and U937) as compared with monocytes or polymorphonuclear cells. Treatment of U937 cells with interferon-gamma up-regulated their APG binding capacity along with the expression of the integrin CD 11 b and the CD 14 molecule, whereas monocytes exposed to interferon-gamma showed an increased binding of APG associated with an elevated expression of the galactose specific lectin Mac-2. The data demonstrate a preferential binding of Kp-MPG and APG to cells of the monocyte/macrophage lineage. APG binding does not involve the poly (1,3) galactose chain and the ester-linked C14 and C16 fatty acids but requires the presence of the hydrophobic part of the molecule.
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PMID:Binding of a membrane proteoglycan from Klebsiella pneumoniae and its derivatives to human leukocytes. 149 Jul 26

This study reports on the earliest stages of mononuclear phagocyte differentiation. A crucial question in this developmental process is whether mature macrophage (M phi) heterogeneity is already appointed at the precursor cell level. For this purpose, we produced clonal populations of mononuclear phagocytes from bone marrow culture by somatic cell hybridization with two hypoxanthine, aminopterin, thymidine-sensitive myeloid cell lines. A panel of 22 stable hybrids was obtained from these fusions. Differentiation stage analysis of the hybrids indicated that all cell lines had immature mononuclear phagocyte characteristics. The hybrids exhibited typical myeloid morphology and mainly nonadherent growth. Mature M phi features, such as expression of the cell surface antigens Mac-1, Mac-2 and F4/80, phagocytosis of latex beads, and expression of nonspecific esterase and acid phosphatase activity, were virtually absent. The immature M phi markers Thy-1, MIV25 and MIV52, on the other hand, were readily expressed, although heterogeneity was observed among different hybrid cell lines. We then analyzed the differentiation potential of seven hybrids by culture of the cells in the presence of post-lipopolysaccharide serum supplemented with interferon-gamma and found that the expression of mature M phi characteristics was induced. However, the various hybrids showed divergent patterns of mature M phi marker induction. R0C2 cells, for instance, showed extensive morphological and phenotypical differentiation without concomitant induction of phagocytosis. In contrast, W1C4 cells showed significant induction of phagocytosis without simultaneous increase of phosphatase and esterase activity. R1C1 cells were unique in the strong induction of Ia antigen expression. Together, our data indicate that (a) early M phi differentiation stages can be rescued by somatic cell hybridization, and that (b) the obtained cell lines are able to mature according to divergent differentiation programs.
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PMID:Murine macrophage precursor characterization. I. Production, phenotype and differentiation of macrophage precursor hybrids. 196 90

A family of beta-galactoside-binding animal lectins has recently been designated as galectins. One member of this family, galectin-3, has been known as epsilon BP for its IgE-binding activity and as Mac-2, a macrophage surface antigen, CBP35, CBP30, L-29, and L-34. Although much information has accumulated on the expression of this lectin in murine macrophages and human monocytic cell lines, little is known about the expression and function of this protein in normal human monocytes/macrophages. We now report that galectin-3 is expressed in normal human peripheral blood monocytes and its level increases dramatically as human monocytes differentiate into macrophages upon culturing in vitro. Immunoblot analysis showed that there was a 5-fold increase in the level of galectin-3 after 1 day of culture and greater than a 12-fold increase after 5 days. Immunocytochemical analysis confirmed this progressive increase of galectin-3 expression in cultured monocytes. Immunogold cytochemistry/electron microscopy analysis revealed that galectin-3 was expressed on the surface of human monocytes and that the level of cell surface galectin-3 increased progressively as these cells differentiated into macrophages. The level of galectin-3 in human monocytes/macrophages was modulated by stimuli such as lipopolysaccharide and interferon-gamma, and galectin-3 was secreted when monocytes were stimulated by calcium ionophore A23187 Soluble galectin-3 caused superoxide release from human monocytes; this activity was dependent on the lectin property of galectin-3, as it was inhibitable by lactose. Thus, galectin-3 may modulate the function of this cell type in an autocrine or paracrine fashion through binding to cell surface glycoconjugates.
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PMID:Expression and function of galectin-3, a beta-galactoside-binding lectin, in human monocytes and macrophages. 757 47

A c-myc retrovirus-transformed myeloid leukemia line, MMB3.19, of C57BL/6 (B6) origin, was developed to investigate graft-versus-leukemia (GVL) activity in murine bone marrow transplantation (BMT) models. It was previously determined that both naive and leukemia-presensitized CD4+-enriched T cells are capable of mediating GVL activity to MMB3.19 challenge in both syngeneic (B6) and allogeneic (C3H.SW-->B6) strain combinations, with the latter coinciding with minimal graft-versus-host disease. In the present study, MMB3.19 and 2 other similarly derived, yet phenotypically diverse, B6 myeloid leukemia lines (MMB1.10 and MMB2.18) were investigated for potential shared tumor antigens in the syngeneic GVL model. Morphologically, all 3 tumor lines are blastic with high cytoplasmic:nuclear ratios, but MMB2.18 displays dendritic processes, whereas MMB1.10 and MMB3.19 have a more rounded appearance. Flow cytometric analysis of the 3 lines revealed constitutive surface molecule expression of Mac-1, Mac-2, F4/80, LFA-1, B7-1, B7-2, H2Kb, H2Db, and macrophage scavenger receptor, consistent with macrophage/monocyte lineages. Furthermore, each of the lines expresses H2I-Ab, but to varying degrees, with MMB2.18 cells having the lowest percentage (31.6%). In vitro 51Cr release assays using MMB3.19-primed T-cell effectors demonstrated equivalent specific lysis of all 3 leukemia-line target cells. In addition, enzyme-linked immunospot analysis of MMB3.19-primed CD4+ T cells revealed significantly increased frequencies of tumor-stimulated interleukin (IL)-2-, IL-4-, and interferon-gamma-secreting cells when restimulated with each of the 3 leukemia lines. Furthermore, when MMB3.19-primed CD4+ T cells were administered in a BMT setting, a protective GVL effect was seen in those mice challenged with MMB1.10, MMB2.18, or MMB3.19. Therefore, in vitro and in vivo experiments indicate that the 3 distinct myeloid leukemia lines share 1 or more common major histocompatibility complex class II-restricted tumor antigens that can elicit a cross-protective in vivo T-cell GVL response.
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PMID:Cross-protective murine graft-versus-leukemia responses to phenotypically distinct myeloid leukemia lines. 1107 Dec 59

Osteopontin (OPN) expression in tumors is associated with more aggressive tumor growth; however, several studies have suggested that OPN as a host protein can regulate tumor growth as well. OPN is produced by macrophages and T cells, and reportedly modifies macrophage function. Here, we have investigated the effect of OPN on macrophage function, and its role in host defense against tumor growth. OPN deficient (-/-) and wild-type (WT) peritoneal macrophages were assessed for their ability to mediate cytotoxicity of tumor cells. Thioglycollate-elicited peritoneal exudate cells (PEC) were stimulated in vitro with interferon-gamma and lipopolysaccharide. [(3)H]Thymidine-labeled ras-transformed tumor cells were then added and (3)H release and nitrite accumulation were measured. OPN -/- PEC exhibited as much as a 70% reduction in cytotoxicity as compared to WT PEC. Tumor cell OPN status, on the other hand, had little effect on the extent of cytotoxicity. Production of nitrite by the PEC correlated with their capacity to kill tumor cells. L-929 cells, which are relatively resistant to nitric oxide-induced cytotoxicity and sensitive to that effected by TNF-alpha, were killed equally well by wild-type and OPN-deficient PEC, suggesting that the effect of OPN is not mediated through TNF-alpha. No difference was seen in the cytotoxicity of resident macrophages from mice of different genotypes, indicating that the defect in the OPN-deficient macrophages may result from altered differentiation in vivo. In support of this idea, we show that the expression of the macrophage markers F4/80 in peritoneal cells and of Mac-2 in spleen cells is altered in OPN -/- mice as compared to WT. These data support the hypothesis that host-derived osteopontin may inhibit tumor growth and provide a mechanism for this effect.
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PMID:Impaired anti-tumor cytotoxicity of macrophages from osteopontin-deficient mice. 1505 10

Macrophages have been proposed as a key cell type in the pathogenesis of renal fibrosis; however, the mechanism by which macrophages drive fibrosis is still unclear. We show that expression of galectin-3, a beta-galactoside-binding lectin, is up-regulated in a mouse model of progressive renal fibrosis (unilateral ureteric obstruction, UUO), and absence of galectin-3 protects against renal myofibroblast accumulation/activation and fibrosis. Furthermore, specific depletion of macrophages using CD11b-DTR mice reduces fibrosis severity after UUO demonstrating that macrophages are key cells in the pathogenesis of renal fibrosis. Disruption of the galectin-3 gene does not affect macrophage recruitment after UUO, or macrophage proinflammatory cytokine profiles in response to interferon-gamma/lipopolysaccharide. In addition, absence of galectin-3 does not affect transforming growth factor-beta expression or Smad 2/3 phosphorylation in obstructed kidneys. Adoptive transfer of wild-type but not galectin-3(-/-) macrophages did, however, restore the fibrotic phenotype in galectin-3(-/-) mice. Cross-over experiments using wild-type and galectin-3(-/-) macrophage supernatants and renal fibroblasts confirmed that secretion of galectin-3 by macrophages is critical in the activation of renal fibroblasts to a profibrotic phenotype. Therefore, we demonstrate for the first time that galectin-3 expression and secretion by macrophages is a major mechanism linking macrophages to the promotion of renal fibrosis.
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PMID:Galectin-3 expression and secretion links macrophages to the promotion of renal fibrosis. 1820 87

Galectin-3 belongs to a family of beta-galactoside-binding animal lectins expressed in several cell types, including epithelial and immune cells. To establish the role of galectin-3 in the development of allergic skin inflammation, we compared inflammatory skin responses of galectin-3-deficient (gal3(-/-)) and wild-type (gal3(+/+)) mice to epicutaneous sensitization with ovalbumin (OVA). OVA-treated gal3(-/-) mice exhibited markedly reduced epidermal thickening, lower eosinophil infiltration, and lower serum IgE levels compared with gal3(+/+) mice. The former evoked lower interleukin-4, but higher interferon-gamma, mRNA expression at OVA-treated skin sites. Moreover, gal3(-/-) splenocytes from OVA-sensitized mice secreted more interleukin-12 compared with gal3(+/+) splenocytes. In addition, antigen presentation by gal3(-/-) dendritic cells to T cells in vitro were T helper cell (Th1)-polarized relative to presentation by gal3(+/+) dendritic cells. When exposed to OVA, recipients engrafted with T cells from gal3(-/-) OVA-specific T cell receptor transgenic mice developed significantly reduced dermatitis and a markedly lower Th2 response compared with recipients of comparable gal3(+/+) T cells. We conclude that galectin-3 is critical for the development of inflammatory Th2 responses to epicutaneously administered antigens; in its absence, mice develop a Th1-polarized response. This regulatory effect of galectin-3 on Th development is exerted at both the dendritic cell and T cell levels. Our studies suggest that galectin-3 may play an important role in the acute phase of human atopic dermatitis.
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PMID:Galectin-3 is critical for the development of the allergic inflammatory response in a mouse model of atopic dermatitis. 1917 12

Galectins, a family of animal lectins, are involved not only in development and differentiation but also in immunoregulation and host-pathogen interactions. Galectin-3 interacts with lipopolysaccharides in gram-negative bacteria such as Escherichia coli, Salmonella minnesota and Pseudomonas aeruginosa. The present study investigated whether galectin-3 inhibited the cytokine-inducing activity of periodontopathic bacterial lipopolysaccharides using splenocytes derived from mice of different ages. Lipopolysaccharides were extracted from Aggregatibacter actinomycetemcomitans Y4 and Porphyromonas gingivalis ATCC 33277, and then purified. Enzyme-linked immunosorbent assay (ELISA) analysis revealed that galectin-3 adhered to A. actinomycetemcomitans lipopolysaccharides, but not to the lipopolysaccharides of P. gingivalis. Splenocytes were prepared from 1- or 7-month-old C57BL/6 mice. Either A. actinomycetemcomitans lipopolysaccharides (200 ng mL(-1)) alone or lipopolysaccharides and murine galectin-3 (10 microg mL(-1)) were added to culture solutions, and the release of interleukin-6 (IL-6) and interferon-gamma (IFNgamma) from splenocytes was measured by ELISA after a 17-h incubation. In all mice tested, A. actinomycetemcomitans lipopolysaccharide stimulation significantly increased the production of IL-6 and IFNgamma (P<0.01). Murine galectin-3 suppressed lipopolysaccharide-induced cytokine production in the splenocytes of the 1-month-old mice (P<0.02 for IL-6; P<0.05 for IFNgamma), but not in the splenocytes of the 7-month-old mice. This suggests that responses change with age.
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PMID:Inhibitory effect of galectin-3 on the cytokine-inducing activity of periodontopathic Aggregatibacter actinomycetemcomitans endotoxin in splenocytes derived from mice. 1961 43

Cyclophilin C-associated protein (CyCAP) or Mac-2 binding protein has been identified as a binding protein for cyclophilin C in mice and for Mac-2 (galectin-3) in human, suggesting its multiple binding activity to proteins. In the present study, using specific anti-rat-CyCAP antibody, we found that CyCAP colocalizes with calnexin at the location near the nuclear envelope, however CyCAP does not have colocalization with calreticulin. In senescent fibroblasts and interferon-gamma (IFNgamma) treated fibroblasts, both calnexin and CyCAP form larger polymers and are released from the endoplasmic reticulum (ER) through the cellular membrane to the extracellular area. Immunoprecipitation studies further confirm that the release of calnexin is through binding to CyCAP. Further, we found that tissue transglutaminase (tTG) protein is decreased, however not at the RNA level, in CyCAP null fibroblasts, which suggests that CyCAP is involved in tTG post-translational modification. Our data give novel evidence that CyCAP regulates the post-translational modification of tTG through its colocalization with calnexin in ER.
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PMID:Cyclophilin C-associated protein/Mac-2 binding protein colocalizes with calnexin and regulates the expression of tissue transglutaminase. 2004 54